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The Latest Alzheimer's Research


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#1 Mind

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Posted 11 July 2008 - 09:12 PM


Blood pressure may increase dementia risk

Two studies support a link between high blood pressure and dementia risk - with one by an Imperial College London team suggesting treatment could cut this.

This study, by published in the Lancet Neurology journal, found blood pressure drugs reduce dementia by 13%.

The Alzheimer's Society said better control could save 15,000 lives a year. "Only half of people over 65 receive effective treatment, yet we know treatment works" - Professor Clive Ballard, Alzheimer's Society

As many as one in four people has high blood pressure, in many cases undiagnosed or untreated.

The precise reasons why high blood pressure might increase the risk of dementia are not fully understood although many scientists believe that it can starve the brain of bloodflow and the oxygen it carries.


Amyloid beta implicated once again

Alzheimer's disease constitutes a rising threat to public health. Despite extensive research in cellular and animal models, identifying the pathogenic agent present in the human brain and showing that it confers key features of Alzheimer's disease has not been achieved. We extracted soluble amyloid-beta protein (A-beta) oligomers directly from the cerebral cortex of subjects with Alzheimer's disease. The oligomers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus. Soluble A-beta from Alzheimer's disease brain also disrupted the memory of a learned behavior in normal rats. These various effects were specifically attributable to A-beta dimers. Mechanistically, metabotropic glutamate receptors were required for the LTD enhancement, and N-methyl D-aspartate receptors were required for the spine loss. Co-administering antibodies to the A-beta N-terminus prevented the LTP and LTD deficits, whereas antibodies to the midregion or C-terminus were less effective. Insoluble amyloid plaque cores from Alzheimer's disease cortex did not impair LTP unless they were first solubilized to release A-beta dimers, suggesting that plaque cores are largely inactive but sequester A-beta dimers that are synaptotoxic. We conclude that soluble A-beta oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species.



#2 Mind

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Posted 21 July 2008 - 08:23 PM

Another potential treatment?

TNF-alpha, a critical component of the brain's immune system, normally finely regulates the transmission of neural impulses in the brain. The authors hypothesize that elevated levels of TNF-alpha in Alzheimer's disease interfere with this regulation. To reduce elevated TNF-alpha, the authors utilized a unique perispinal delivery method to administer etanercept.


Unfortunately, this is not a clinical trial

According to the lead author of the study, Edward Tobinick, "There are limitations to the data presented; the clinical trial was open label, and not controlled. These caveats notwithstanding, the scientific rationale for the further investigation of anti-TNF-alpha treatment of Alzheimer's disease is compelling. In addition, family members, independent neurologists, and other independent observers have confirmed the clinical, cognitive, and behavioral improvement noted".


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#3 DaffyDuck

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Posted 21 July 2008 - 11:27 PM

TNF-alpha, a critical component of the brain's immune system, normally finely regulates the transmission of neural impulses in the brain. The authors hypothesize that elevated levels of TNF-alpha in Alzheimer's disease interfere with this regulation. To reduce elevated TNF-alpha, the authors utilized a unique perispinal delivery method to administer etanercept.


Here is a video showing an "awakening" by a woman with advanced alzheimers who is tested without and with etanercept. It's really cool to see. I use the term awakening because it reminds me of the dramatic effect of L-Dopa in the movie Awakenings.



Also, here's a link to the research article that goes along with this.

http://www.biomedcen...7/8/27/abstract

Edited by DaffyDuck, 21 July 2008 - 11:30 PM.

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#4 Zenob

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Posted 16 November 2008 - 04:30 AM

Dr. Lukiw's lab at the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence has shown that this tiny piece of RNA, or microRNA, called miRNA-146a is found in increased amounts in stressed human brain cells and in Alzheimer's disease, and that it plays a crucial role in the regulation of inflammation and disease-related neuropathology thought to be integral to the Alzheimer's disease process.
Link

I thought the main culprit of Alzheimer's Disease was amyloid beta. I didn't know there was an inflammation component to it. Maybe miRNA-146a plays some part in reduced clearance or increased production of amyloid beta that causes the disease by over whelming the cells ability to clear it.

#5 Mind

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Posted 18 November 2008 - 11:42 PM

tau tangles more numerous in Alzheimer's patients

Scientists examined the brains of five deceased people considered super aged because of their high performance on memory tests when they were more than 80 years old and compared them to the brains of elderly, non-demented individuals. Researchers found the super aged brains had many fewer fiber-like tangles than the brains of those who had aged normally. The tangles consist of a protein called tau that accumulates inside brain cells and is thought to eventually kill the cells. Tangles are found in moderate numbers in the brains of elderly and increase substantially in the brains of Alzheimer's disease patients.

"This new finding in super aged brains is very exciting," said Changiz Geula, principal investigator of the study and a research professor of neurology at the Cognitive Neurology and Alzheimer's Disease Center at Northwestern's Feinberg School. "It was always assumed that the accumulation of these tangles is a progressive phenomenon through the aging process. But we are seeing that some individuals are immune to tangle formation and that the presence of these tangles seems to influence cognitive performance." Individuals who have few tangles perform at superior levels, while those who have more tangles appear to be normal for their age, Geula noted.



#6 VictorBjoerk

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Posted 18 November 2008 - 11:56 PM

isn't high insulin a problem in alzheimers?. I mean high insulin surpresses the body's natural repair mechanism/removal system of amyloids and the body removes them more and more ineffective...

#7 100YearsToGo

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Posted 19 November 2008 - 10:33 PM


http://www.imminst.o...showtopic=25586

#8 Mind

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Posted 07 January 2009 - 09:43 PM

New PET scan technique reveals amount of plaque in the brain

Nice technique to evaluate new therapies coming on to the market (maybe this one) and perhaps to see what if any effect different diets (or supps like resveratrol) have on brain aging.

Researchers used positron emission tomography (PET), which allows "a window into the brain" of living people and specifically reveals plaques and tangles, the hallmarks of neurodegeneration. The PET scans were complemented by information on patients' age and congnitive status and a genetic profile.

"Combining key patient information with a brain scan may give us better predictive power in targeting those who may benefit from early interventions, as well as help test how well treatments are working," said study author Dr. Gary Small, who holds UCLA's Parlow-Solomon Chair on Aging and is a professor at the Semel Institute for Neuroscience and Human Behavior at UCLA.

Scientists took PET brain scans of 76 non-demented volunteers after they had been intravenously injected with a new chemical marker called FDDNP, which binds to plaque and tangle deposits in the brain. Researchers were then able to pinpoint where these abnormal protein deposits were accumulating.

They reported that older age correlated with higher concentrations of FDDNP in the medial and lateral temporal regions of the brain, areas involved with memory, where plaques and tangles usually collect. The average age of study volunteers was 67.


Edited by Mind, 07 January 2009 - 09:44 PM.


#9 caston

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Posted 08 January 2009 - 02:28 PM

Thanks Mind ;)

Interesting the article talks about "tau tangles". I don't remember hearing of these before.

So what are the main factors in neuro-degeneration then ?

Perhaps:

1) tau protein tangles
2) amyloid plaques
3) demyelination of neuron sheaths

Perhaps there will be more discoveries of small molecules to assist with the above. e.g.

http://www.scienceda...81230074742.htm

Edited by caston, 09 January 2009 - 02:54 AM.


#10 FunkOdyssey

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Posted 08 January 2009 - 03:59 PM

Right now curcumin comes to mind for beta-amyloid, niacinamide for tau protein tangles, and high-dose methylcobalamin to protect myelin and prevent brain atrophy. That's a good start -- if I knew anyone with alzheimer's I would have them serious doses of all three.

Edited by FunkOdyssey, 08 January 2009 - 04:13 PM.


#11 caston

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Posted 09 January 2009 - 03:04 PM

Don't forget cinnamon which I have read is effective against both alzheimer's and type II diabetes.

Edited by caston, 09 January 2009 - 03:06 PM.


#12 AgeVivo

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Posted 01 February 2009 - 08:37 PM

Netrin-1 injection removes amyloid plaques in APP mice

http://www.ncbi.nlm....pubmed/19148186 :
Netrin-1 interacts with amyloid precursor protein and regulates amyloid-beta production.
FC Lourenc, V Galvan, J Fombonne, V Corset, F Llambi, U Mu¨ ller, DE Bredesen and P Mehlen.
Cell Death and Differentiation advance online publication, 16 January 2009; doi:10.1038/cdd.2008.191.

The beta-amyloid precursor protein (APP) is an orphan transmembrane receptor whose physiological role is largely unknown. APP is cleaved by proteases generating amyloid-beta (Abeta) peptide, the main component of the amyloid plaques that are associated with Alzheimer's disease. Here, we show that APP binds netrin-1, a multifunctional guidance and trophic factor. Netrin-1 binding modulates APP signaling triggering APP intracellular domain (AICD)-dependent gene transcription. Furthermore, netrin-1 binding suppresses Abeta peptide production in brain slices from Alzheimer model transgenic mice. In this mouse model, decreased netrin-1 expression is associated with increased Abeta concentration, thus supporting netrin-1 as a key regulator of Abeta production. Finally, we show that netrin-1 brain administration in Alzheimer model transgenic mice may be associated with an amelioration of the Alzheimer's phenotype.



#13 Mind

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Posted 10 February 2009 - 09:50 PM

BDNF protein prevents and reverse Alzheimer's in animal models.

In each case, when compared with control groups not treated with BDNF, the treated animals demonstrated significant improvement in the performance of a variety of learning and memory tests. Notably, the brains of the treated animals also exhibited restored BDNF gene expression, enhanced cell size, improved cell signaling, and activation of function in neurons that would otherwise have degenerated, compared to untreated animals. These benefits extended to the degenerating hippocampus where short-term memory is processed, one of the first regions of the brain to suffer damage in Alzheimer's disease.


Anyone have any other information about BDNF?

The protective and restorative effects of BDNF occurred independently of the build-up of amyloid, a protein that accumulates in the brain to form plaques in Alzheimer's disease. Many current experimental treatments for Alzheimer's disease target amyloid production, so the potential role of BDNF as an alternative protective intervention is of great potential interest, said Tuszynski. Because BDNF targets a different set of disease mechanisms than amyloid modulation, there is also potential to combine BDNF and amyloid-based treatments, theoretically providing a two-pronged attack on the disease.


Seems like a lot of new therapies to attack Alzheimer's are in the works. Netrin-1, BDNF, NGF, Elan's immunological approach, etc... Hope to see some human results soon.

#14 JLL

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Posted 11 February 2009 - 10:38 AM

Intermittent fasting and caloric restriction increase BDNF.

Dietary restriction (DR) increases the lifespan of rodents and increases their resistance to several different age-related diseases including cancer and diabetes. Beneficial effects of DR on brain plasticity and neuronal vulnerability to injury have recently been reported, but the underlying mechanisms are unknown. We report that levels of brain-derived neurotrophic factor (BDNF) are significantly increased in the hippocampus, cerebral cortex, and striatum of rats maintained on a DR regimen compared to animals fed ad libitum (AL). Seizure-induced damage to hippocampal neurons was significantly reduced in rats maintained on DR, and this beneficial effect was attenuated by intraventricular administration of a BDNF-blocking antibody. These findings provide the first evidence that diet can effect expression of a neurotrophic factor, demonstrate that BDNF signaling plays a central role in the neuroprotective effect of DR, and proffer DR as an approach for reducing neuronal damage in neurodegenerative disorders.


http://www.springerl...n664k411733634/

EDIT: I can't seem to find the study I was looking for; but there was one where IF had better results than CR in terms of increasing BDNF.

Edited by JLL, 11 February 2009 - 10:45 AM.


#15 Michael

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Posted 12 February 2009 - 04:12 PM

Intermittent fasting and caloric restriction increase BDNF.

http://www.springerl...n664k411733634/

Preliminary evidence suggests that Calorie restriction increases BDNF levels in humans, too, although the study is very preliminary and only looks at circulating BDNF. This is consistent with CR's widely-documented antianxiety and euphoric or antidepressant effects in rodents and (apparently) humans
.

EDIT: I can't seem to find the study I was looking for; but there was one where IF had better results than CR in terms of increasing BDNF.

I won't bother looking it up, but Mattson's group have reported this, yes. In general, IF seems to be somewhat more protective than consistent daily CR in protecting the brain against acute neurotoxic attack, too, which is consistent with this. However, alternate-day fasting without a concommitant reduction in Calories consumed fails to retard aging or extend lifespan in rodents, and seems not to give the standard CR benefits in humans on blood pressure, body temperature, or cholesterol profile;(1) nor on glucose metabolism (1-3); nor on circulating BDNF (3). Consistent with this last, "many reported feeling irritable on their fasting days, " (4) which seems potentially to suggest a lack of happy-making BDNF. On the other hand, plenty of people do report a nice high when fasting, although it often takes several days to occur (at which point, de facto reduction in energy balance is clearly established IAC).

-Michael

References
1. A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults.
Stote KS, Baer DJ, Spears K, Paul DR, Harris GK, Rumpler WV, Strycula P, Najjar SS, Ferrucci L, Ingram DK, Longo DL, Mattson MP.
Am J Clin Nutr. 2007 Apr;85(4):981-8.
PMID: 17413096 [PubMed - indexed for MEDLINE]

2. Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women.Carlson O, Martin B, Stote KS, Golden E, Maudsley S, Najjar SS, Ferrucci L, Ingram DK, Longo DL, Rumpler WV, Baer DJ, Egan J, Mattson MP.
Metabolism. 2007 Dec;56(12):1729-34.
PMID: 17998028 [PubMed - indexed for MEDLINE]

3. Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting.
Heilbronn LK, Civitarese AE, Bogacka I, Smith SR, Hulver M, Ravussin E.
Obes Res. 2005 Mar;13(3):574-81.
PMID: 15833943 [PubMed - indexed for MEDLINE]

4. Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism.
Heilbronn LK, Smith SR, Martin CK, Anton SD, Ravussin E.
Am J Clin Nutr. 2005 Jan;81(1):69-73.
PMID: 15640462 [PubMed - indexed for MEDLINE]

Edited by Michael, 12 February 2009 - 04:59 PM.


#16 JLL

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Posted 12 February 2009 - 04:47 PM

Interesting studies, thanks for posting them.

The first study is kind of disappointing in that it didn't show increases in BDNF (in fact there seemed to be a slight decrease). The impaired glucose tolerance seems a little strange, but as the authors speculate, maybe it was due to the subjects eating a lot in the evening and then having the blood test taken the next morning.

This caught my eye in the second study:

"SIRT1 mRNA expression was increased after alternate day fasting (p = 0.01). The increased expression in SIRT1 suggests that alternate day fasting may improve stress resistance, a commonly observed feature of calorie-restricted rodents."

That'd be good news.

EDIT: Note also that the first study uses the "compressed window" version of IF, not alternate-day feeding or a 24/24 cycle.

Edited by JLL, 12 February 2009 - 04:51 PM.


#17 Mind

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Posted 01 April 2009 - 09:18 PM

Possible Mechanism Of Neurodegeneration In Alzheimer's Disease Discovered

The particles are minute clumps of amyloid beta, which has long been known to accumulate and form plaques in the brain of Alzheimer's patients.

"These small particles that haven't aggregated into plaques—these are increasingly being seen as the really toxic species of amyloid beta," says Scott Brady of University of Illinois College of Medicine, who has been an MBL investigator since 1982.

Brady and his colleagues found that these particles inhibit neurons from communicating with each other and with other target cells in the body.


Just wondering if any of the newest treatments in development (Elan's immune based approach? The LysoSENS approach?) would get rid of the disruptive small particles of amyloid beta mentioned in the article...or would they only remove the accumulated plaque...or would removing the plaque also get rid of the disruptive particles. Perhaps too speculative at this point?

#18 Michael

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Posted 03 April 2009 - 01:02 AM

Possible Mechanism Of Neurodegeneration In Alzheimer's Disease Discovered

The particles are minute clumps of amyloid beta, which has long been known to accumulate and form plaques in the brain of Alzheimer's patients.

"These small particles that haven't aggregated into plaques—these are increasingly being seen as the really toxic species of amyloid beta," says Scott Brady of University of Illinois College of Medicine, who has been an MBL investigator since 1982.

Brady and his colleagues found that these particles inhibit neurons from communicating with each other and with other target cells in the body.


Just wondering if any of the newest treatments in development (Elan's immune based approach? The LysoSENS approach?) would get rid of the disruptive small particles of amyloid beta mentioned in the article...or would they only remove the accumulated plaque...or would removing the plaque also get rid of the disruptive particles. Perhaps too speculative at this point?

It's a good question. It's certainly an emerging consensus that these "oligomeric" Abeta species are responsible for much (most? all?) of the negative effects of Abeta on cognitive function, but even within the category, there are many different oligomeric species (from relatively large ADDLs to very short dimers and trimers) and there is debate about their relative physiological and pathological significance. Studies have shown that there are conformational differences between the different Abeta species, which are picked up with varying affinity by different antibodies (therapeutic and not); moreover, there's significant evidence that (contrary to what the first sentence quoted from Sciencedaily above implies) the plaques are formed from shorter fibrillogenic species ('protofibrils') via a pathway that does not involve these other, soluble oligomers; the truth or falsity of this latter would imply different things about the "sink" view, in which plaque forms a reserve of Abeta that, like a crystal, can slowly leach out oligos, maintaining a high steady-state, and implying that a purely plaque-targeting vaccine could ultimately draw down oligomeric intra- and extraneuronal Abeta. (But then, maybe the "sink" view is right for a different reason: those pesky protofibrils (see recently (1)).

So, there's a lot of open questions. Fortunately, however, there are a lot of Abeta vaccines in the therapeutic pipeline, all of which show at least some efficacy in some models, including several are now in advanced clinical testing -- and we don't necessarily have to know the full mechanistic details of how a therapy works to show, empirically, that it works. Contrary to the negative impression that many of us got from the suspiciously elaborate microdissection of the results presented by Elan in in presenting its latest Phase II trial results with their lead passive vaccine Bapineuzumab suggest that Bapineuzumab is effective disease-modifying therapy against Alzheimer's after all, despite it not apparently having a remarkably high affinity for tested oligomeric species; meanwhile, the little-heard-of Gammagard is also showing promising results in Alzheimer's disease, and there are others coming quickly down the line in human trials, such as CAD 106 and Eli Lilly's LY2062430, and others in (nonhuman primate testing. It may well be that the first generation of vaccines is modestly effective, and we improve iteratively in part by more and more successfully targeting the 'right' Abeta species -- or that a round of different vaccines might be best, regularly targeting soluble species and occasionally removing residual plaque in a progressively more complete rejuvenation of the brain.

Meanwhile, because the oligomeric species initially accumulate intraneuronally and may be processed by lysosomes, and because lysosomal dysfunction is very clearly involved in Alzheimer's, it's indeed reasonable to ask if the LysoSENS approach might work at that end instead/additionally; there's a very intriguing study (2) to suggest that therapeutic vaccines may actually work (in part?) by increasing lysosomal targeting and degradation of Abeta, thereby reducing oligomer burden -- in which case, enhancement/restoration of lysosomal function might itself enhance or render less pressing the effects of such vaccines.

-Michael

References
1. Martins IC, Kuperstein I, Wilkinson H, Maes E, Vanbrabant M, Jonckheere W, Van
Gelder P, Hartmann D, D'Hooge R, De Strooper B, Schymkowitz J, Rousseau F.
Lipids revert inert Abeta amyloid fibrils to neurotoxic protofibrils that affect learning in mice.
EMBO J. 2008 Jan 9;27(1):224-33. Epub 2007 Dec 6.
PMID: 18059472 [PubMed - indexed for MEDLINE]

2. Tampellini D, Magrane' J, Takahashi RH, Li F, Lin MT, Almeida CG, Gouras GK.
Internalized antibodies to the Abeta domain of APP reduce neuronal Abeta and protect against synaptic alterations.
J Biol Chem. 2007 May 1; [Epub ahead of print]
PMID: 17468102 [PubMed - as supplied by publisher]

#19 tunt01

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Posted 22 April 2009 - 07:21 PM

Re: AmyloSENS

Agents That Speed Up Destruction Of Proteins Linked To Alzheimer's Discovered

http://www.scienceda...90421205319.htm

.....

"Historically, a lot of effort has been made at stopping initial production of A-beta in order to halt development of Alzheimer's disease, but we are interested in what happens to A-beta after it is produced," says the study's lead researcher, Malcolm Leissring, Ph.D., from Mayo's Department of Neuroscience.

The researchers found two chemicals that could speed up activity of a molecule, insulin-degrading enzyme (IDE), which helps chew up A-beta proteins produced in the brain.

In laboratory experiments, they found that one agent, dubbed Ia1, increased the activity of IDE by about 700 percent, while the second compound, Ia2, increased it by almost 400 percent.

"This study describes the first examples of synthetic small-molecule activators of IDE, showing that activation of this important enzyme with druglike compounds is achievable," Dr. Leissring says.

"If it is possible to generate drugs for human use that stimulate the activity of IDE, these agents might offer therapeutic benefit for treating and preventing Alzheimer's disease," he says.

Since IDE also chews up excess insulin in the body, the role for which it is primarily known, small molecule activators might also be useful in controlling diabetes, he says.

#20 maestro949

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Posted 26 April 2009 - 04:43 PM

Still more research needed but here's an example where the symptoms were treated without targeting the amyloids.

Brain-Derived Neurotrophic Factor Reverses Memory Loss and Cognitive Impairment in Animal Models of Aging and Alzheimer Disease

ARTICLE IN BRIEF

Gene delivery of brain-derived neurotrophic factor to the entorhinal cortex prevented or reversed memory loss, cognitive impairment, brain cell degeneration, and cell death in a transgenic mouse model of Alzheimer disease, as well as aged mouse and non-human primate models.

Intriguing new research points to the key role that brain-derived neurotrophic factor (BDNF) plays in neuron survival and synaptic health in rodent and non-human primate models of Alzheimer disease (AD).

Mark H. Tuszynski, MD, PhD, professor of neurosciences and director of the Center for Neural Repair at the University of California-San Diego (UCSD), his team in San Diego, and colleagues from the University of California-Los Angeles (UCLA) and New York University, reported in a Feb. 8 paper posted online ahead of the print version of Nature Medicine that gene delivery of BDNF to the entorhinal cortex prevented or reversed memory loss, cognitive impairment, brain cell degeneration, and cell death in a transgenic mouse model of AD, as well as aged rats, rats with induced damage to the entorhinal cortex, aged rhesus monkeys, or monkeys with entorhinal cortex damage.

What is most striking about this work is that it uses animal models that are related to Alzheimer disease, said Vassilis Koliatsos, MD, associate professor of neuropathology at Johns Hopkins University, who was not involved with the Tuszynski study. Where the nerve cells would otherwise become atrophic, BDNF makes them larger. And it helps preserve synapses.

The results need to be replicated, he cautioned, as did others who commented on the study. Additionally, they noted that animal models of AD are not exact replicas of the human disease, making clinical trials a must.

A member of the neurotrophin family of proteins, BDNF is important during development and adult life for neuronal growth, survival, differentiation, and synaptic function of the entorhinal cortex and hippocampus.

Previous studies had shown that both precursor and mature levels of BDNF are decreased in the brains of people with mild cognitive impairment (MCI) and mild AD. With this in mind, Dr. Tuszynski's team first examined whether BDNF would affect a transgenic mouse model that expresses the human amyloid precursor protein (APP) transgene. Over successive daily trials, spatial memory deficits improved significantly and performance was enhanced on a fear-conditioning test in the BDNF-treated mice. Controls were age-matched with wild-type littermates who underwent sham surgery.

GOOD RESULTS IN SPITE OF AMYLOID


The protective and restorative effects of BDNF occurred in the mice, independent of the amount of amyloid deposited.

This is an important finding because it suggests, as a lot of research has suggested, that amyloid may not be the primary cause of behavior problems that you see in Alzheimer patients, said Elliott Mufson, PhD, Rush University Professor of Neurological Sciences, who was not affiliated with the Nature Medicine study.

Dr. Koliatsos agreed, noting that this comes at a time when amyloid, the predominant target of therapy for Alzheimer disease, has not given us great therapeutic products or solutions.


Dr. Mufson added that in AD, among the earliest areas to be affected with nerve fibrillary tangles are the entorhinal cortex neurons. Those structures were targeted by the Tuszynski group in their studies.

After the transgenic mice were treated with BDNF, the researchers assessed spatial learning and memory in 36 young and 37 aged rats, of which 81 percent showed baseline cognitive impairment. BDNF infusions given in the medial entorhinal cortex significantly improved spatial learning and memory on all measures of water maze performance.

To determine if BDNF prevented the death of entorhinal neurons, the researchers caused cell death with amyloid-beta1-42 in rat entorhinal neurons. BDNF treatment concurrent with the cell-death agent prevented neuron death and ameliorated cell atrophy.

To study the restorative effects of BDNF in non-human primate models of entorhinal cortex neuronal death, the team injected lentiviral vectors expressing BDNF into the right entorhinal cortex of six rhesus monkeys and compared the results to injections of Lenti-green florescent protein (GFP) in the left entorhinal cortex of four of the six monkeys, and no virus into the left entorhinal cortex of two of the monkeys.

Stereological quantification - a three-dimensional study of the tissue - showed loss of neurons in the non-BDNF areas while BDNF significantly prevented lesion-induced entorhinal neuronal death. A final experiment examined the effects of BDNF gene delivery to the entorhinal cortex in nine aged monkeys with impaired visuospatial learning. Four received BDNF and five GFP, targeting entorhinal cortex neurons projecting to the hippocampus. When tested on the visuospatial discrimination task, BDNF-treated aged monkeys showed significant improvement.

PREVIOUS BDNF WORK

Studies of BDNF and cognitive decline are not new. In the early 1990s, several laboratories studied neurotrophic factors, including BDNF, trying to match up specific proteins with specific nerve cells. However, either because the disease was too advanced already or it was the way the trophic factor was given to the nervous system, clinical trials that resulted from these studies were not successful, noted Dr. Koliatsos, who has conducted BDNF research. We also had the problem of bioavailability - how biologically available these proteins become to neural targets if you give them.

Dr. Koliatsos was impressed with Dr. Tuszynski's idea to genetically engineer vectors for delivery of the BDNF into the entorhinal cortex and to produce a constant supply of the nourishing neurotrophin. He put the cells where they would secrete this peptide and have a local fresh supply where it matters.

Dr. Tuszynski had used this same delivery method in previous work surgically delivering another neurotrophic factor - nerve growth factor (NGF) - into the brains of AD patients. In a 2005 Nature Medicine paper, he showed that NGF stimulated cholinergic function, improved memory, and prevented cholinergic degeneration in animal models and proved safe in eight human subjects. The team reported that cognitive tests suggested improvement in the patients following NGF therapy. This approach is now being tested in phase 2 trials at centers throughout the country.

NGF therapy aims to stimulate the function of specific cholinergic neurons, which are like the air traffic controllers of the brain, helping to direct the activities of cells in broad regions of the brain, Dr. Tuszynski explained. However, he added that the benefits of NGF therapy will not be curative.

In contrast, he said, BDNF acts directly on dying cells in specific memory circuits of the brain and might provide long-lasting protection by slowing, or even stopping, disease progression in the cortical regions that receive treatment.

However, BDNF has been known to cause adverse effects, including sensory disturbance, pain, nausea and weight loss, and even mood changes. To avoid those side effects, we limit the delivery of the growth factor directly to the entorhinal cortex and hippocampus without allowing it to spread to other areas of the central nervous system, Dr. Tuszynski said.

In the Nature Medicine paper, he and his team directly addressed the concern of weight loss. Using his surgical infusion method of genetically engineered gene delivery, none of the animal models receiving BDNF experienced any weight loss.

In addition to continuing studies with BDNF alone, it would be worthwhile to test BDNF in combination with anti-amyloid therapy, Dr. Tuszynski said. He added that his next steps with BDNF are to conduct long-term safety, toxicity, and dosing studies in rats and non-human primates, in preparation for possible clinical trials, but that will not likely happen for a few more years.

REFERENCES

Nagahara AH, Merrill DA, Tuszynski MH, et al. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.

Holmes C, Boche D, Nicoll JA, et al. Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial.

Peng S, Wuu J, Fahnestock M, et al. Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease.

Koliatsos VE, Clatterbuck RE, Price DL, et al. Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo.

Koliatsos VE, Price DL, Winslow JW, et al. Highly selective effects of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 on intact and injured basal forebrain magnocellular neurons.


Brain-Derived Neurotrophic Factor Reverses Memory Loss and Cognitive Impairment in Animal Models of Aging and Alzheimer Disease

#21 Mind

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Posted 26 April 2009 - 05:30 PM

From my layman's perspective regarding this latest research result, I wonder if the BDNF made the neurons stronger or enhanced their ability to communicate, and thus helped reduce the cognitive impairment. To me, it still seems very important to clear out the amyloid-beta since we are not born with massive amounts clumped all over our brains, but we end up with that situation late in life. Maintaining proper functions with a dwindling number of neurons is great progress, but more optimal would be to keep as many neurons as possible and get rid of the amyloid-beta.

#22 tunt01

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Posted 26 April 2009 - 05:39 PM

I mostly agree.

I look at BDNF / NGF as the hormonal response to repairing a brain and increasing neurogenesis, similar to HGH and other growth factors on a system wide basis. I think the questions are:

- Is there more elegance in keeping all the neurons running right in the first place, such that we maybe prevent future AD/Parkinsons damage? Is the insulin-degrading enzyme (IDE) as described above a method of improving the removal of extracellular junk, similar to how De Cuervo's discovery re: Autophagy improve the removal of intracellular junk?

- If (IDE) and maintaining existing function is not the primary choice (ie. we have AD or brain damage of some sort) -- what are the risks in using BDNF/NGF and these kinds of hormones for brain repair? Are we increasing neuro genesis but risking brain cancer (trading one problem for another)? I don't know what the trade-off is, but it would be nice to know.

I'd like to know what dosage and interval Dr. Levi-Montalcini used for her NGF.

Edited by prophets, 26 April 2009 - 05:47 PM.


#23 maestro949

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Posted 26 April 2009 - 05:55 PM

From my layman's perspective regarding this latest research result, I wonder if the BDNF made the neurons stronger or enhanced their ability to communicate, and thus helped reduce the cognitive impairment. To me, it still seems very important to clear out the amyloid-beta since we are not born with massive amounts clumped all over our brains, but we end up with that situation late in life. Maintaining proper functions with a dwindling number of neurons is great progress, but more optimal would be to keep as many neurons as possible and get rid of the amyloid-beta.


Right but the key point is that simply removing the amyloids alone may not be sufficient to treat the ravages of aging. There's still a lot that needs to be flushed out here but upgregulating the neurotrophic factors seems to be the more effective measure according to this paper.

#24 Mind

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Posted 30 April 2009 - 05:04 PM

A positive perspective on the pace of Alzheimer's research and future treatments.

"A ton of work is being done in the field," says Dr. Maria Carrillo, director of Medical and Scientific Relations for the Alzheimer's Association. "We are on the hunt for early detection tests that can be done in a general practitioner's office. And as far as medicines are concerned, we're looking at a very robust pipeline."

Alzheimer's, the most common form of dementia, afflicts as many as 5.2 million Americans. And as the population ages, the Alzheimer's Association expects half a million new cases a year, with 10 million baby boomers eventually developing the degenerative disease that is fatal. Mass marketing a test to identify the disease before patients develop clinical symptoms means that therapies, including drugs, may be able to stop the progression and preserve normal functions.

"I can't stress enough the importance of diagnosing early," says Dr. Richard Isaacson, director of the Alzheimer's Division at the University of Miami at the Leonard M. Miller School of Medicine. "The earlier we find out, the better the patient will do."

Isaacson and his staff recently launched a clinical trial looking at the amino acid, BMAA, in hair samples of Alzheimer patients and a control group. They are hoping to determine if the presence of this amino acid is a predictive of the disease, or a result of the degenerative process itself.

There is also hopeful talk of a vaccine. "In the vaccine trials, we are asking: Are there ways to immunize people to prevent accumulation of amyloid plaque?" says Dr. Ralph Sacco, chairman of University of Miami's Department of Neurology. "How much of memory loss is preventable?"



#25 Mind

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Posted 04 May 2009 - 11:15 PM

Mechanisms That Prevent Alzheimer's Disease: Enzymatic Activity Plays Key Role.

In a project involving the collaboration of several institutes, research scientists of the Johannes Gutenberg University Mainz have succeeded in gaining further insight in the functioning of endogenous mechanisms that protect against the development of Alzheimer's disease. It was found that the activity of the enzyme α-secretase is mainly responsible for the protective effect.


"The α-secretase enzyme is a highly complex one, with many other functions. For example, it also relays signals from the intercellular space into cells and interacts with molecules on other cells." Fahrenholz and his colleagues have now established, following investigations in a transgenic mouse model, that it is the enzymatic activity alone that guarantees the protective effects. If this activity is neutralised, the laboratory mice exhibit the symptoms that are characteristic of Alzheimer's disease: impaired learning ability, poor memory capacity and the build-up of Aβ plaques. It is thus possible that the enzymatic activity of α-secretase could represent the starting point for the development of future treatments.

At the same time, the researchers were able to confirm with their experiments that it is not the plaque build-up itself that is responsible for the loss of memory capacity. The cytotoxic substances that accumulate in plaques only destroy neuron synapses when they are still in solution. Prof. Fahrenholz concludes: "It is important to consider other aspects in addition to the plaques themselves, particularly their precursors, which are a real cause of the disease."


That is a fairly bold statement ("real cause"), but more data is pointing to at least a combination of things responsible for Alzheimer's not just the A-beta plaque. This was discussed toward the end of the interview with Kelsey Moody on the Sunday Evening Update May 3rd.

#26 Lufega

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Posted 05 May 2009 - 02:15 AM

Right now curcumin comes to mind for beta-amyloid, niacinamide for tau protein tangles, and high-dose methylcobalamin to protect myelin and prevent brain atrophy. That's a good start -- if I knew anyone with alzheimer's I would have them serious doses of all three.


Would niacin also work for tau proteins??
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#27 Michael

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Posted 05 May 2009 - 03:30 PM

Still more research needed but here's an example where the symptoms were treated without targeting the amyloids.


I wonder if the BDNF made the neurons stronger or enhanced their ability to communicate, and thus helped reduce the cognitive impairment. [...] Maintaining proper functions with a dwindling number of neurons is great progress, but more optimal would be to keep as many neurons as possible and get rid of the amyloid-beta.

Right but the key point is that simply removing the amyloids alone may not be sufficient to treat the ravages of aging. There's still a lot that needs to be flushed out here but upgregulating the neurotrophic factors seems to be the more effective measure according to this paper.

I think that it's uncontroversial "that simply removing the amyloids alone may not be sufficient to treat the ravages of aging": just confining ourselves to the brain, we also need to remove NFTs and a range of other intracellular and lysosomal inclusions, obviate mitochondrial mutations, and replace existing and inevitable occasional ongoing cell loss; moreover, the brain is of course affected by the systemic effects of aging elsewhere in the body on redox tone and inflammation, so to fully rejuvenate the brain will entail fully rejuvenating the rest of the body. But I think that the idea that an agent to protect cells from the toxic effects of aging damage is ultimately superior to repairing that damage is somewhat implausible on its face: certainly, BDNF might be a good short-term, stopgap measure, but it can only reduce the damaging effects, not eliminate them, whereas removing the underlying damage removes the secondary effects of that damage gratis. Moreover, as Aubrey regularly emphasizes, dynamic metabolic pathways like the ones regulating BDNF are 'set' where they are for a reason, and overriding those regulatory pathways inevitably carries risks; in the case of boosting BDNF, the most obvious one would be cancer, since many cancers (including, in particular, neuroblastomas in the brain) exploit the BDNF signaling pathway to help them resist apoptotic signaling and increase needed vascularization:

The neurotrophic receptor tyrosine kinase TrkB, while binding its high affinity ligand brain-derived neurotrophic factor (BDNF), will play an essential role for nervous system development, neuronal survival, differentiation, and maintenance. However, accumulating evidences implies that TrkB signal pathway may also be involved in a variety of human cancers, in which TrkB is likely to play a role in initiation and metastasis of carcinomas. Overexpression of TrkB is often correlated with the tumorigenesis, angiogenesis and drug resistance in these malignancies, contributing significantly to the metastasis and aggressive phenotype of these poor prognosis tumors. The evidences to show the significant contribution of TrkB to malignancy not only came from solid tumors such as neoblastoma, pancreas cancer, Wilm's tumor and hepatocarcinoma, but also came from haematological malignancies ... Emerging data have suggested that TrkB may be a mediator as well as a marker of carcinogenesis and metastasis, therefore TrkB may be used as a valuable target for cancer therapy especially for the metastatic tumors with poor prognosis.(1)


TRK-B encodes a tyrosine kinase that binds to brain-derived neuotrophic factor (BDNF), as well as neurotrophin-3 (NT-3) and NT-4/5. We have studied the N-myc-amplified human neuroblastoma cell line, SMS-KCN, which expresses both TRK-B and BDNF. Exogenous BDNF induces tyrosine phosphorylation of TRK-B ... In addition, BDNF appears to promote cell survival and neurite outgrowth. ... [Of] a series of 74 primary neuroblastomas, 36% express TRK-B mRNA, 68% express BDNF mRNA, and 31% express both. Truncated TRK-B appears to be preferentially expressed in more-differentiated tumors (ganglioneuromas and ganglioneuroblastomas), whereas full-length TRK-B is expressed almost exclusively in immature neuroblastomas with N-myc amplification. Our findings suggest that in TRK-B-expressing human neuroblastomas, BDNF promotes survival and induces neurite outgrowth in an autocrine or paracrine manner. The BDNF/TRK-B pathway may be particularly important for growth and differentiation of neuroblastomas with N-myc amplification.(2)


I also think that there's been some confusion on one particular point:

upgregulating the neurotrophic factors seems to be the more effective measure according to this paper.

They actually don't say anything to indicate that; I think that you misunderstood the import of one passage (and, actually, the researchers themselves may also not have been thinking clearly on the point):

The protective and restorative effects of BDNF occurred in the mice, independent of the amount of amyloid deposited.

This is an important finding because it suggests, as a lot of research has suggested, that amyloid may not be the primary cause of behavior problems that you see in Alzheimer patients, said Elliott Mufson, PhD, Rush University Professor of Neurological Sciences, who was not affiliated with the Nature Medicine study.

Dr. Koliatsos agreed, noting that this comes at a time when amyloid, the predominant target of therapy for Alzheimer disease, has not given us great therapeutic products or solutions.

On that first bit, (a) the fact that BDNF is effective "independent of the amount of amyloid deposited" isn't evidence that Abeta isn't a major contributor to AD, or that its removal isn't central to its arrest and ultimate reversal; rather, it's again evidence for what has actually been the dominant model for much of the last decade: that the smaller, soluble oligomeric Abeta species, rather than the deposited, fibrillar plaque, is the critical Abeta species (though the plaque is unlikely to be helpful except as a dispensible 'sink'). Similarly on the alpha-secretase experiment:

Mechanisms That Prevent Alzheimer's Disease: Enzymatic Activity Plays Key Role.

[Scientists] have succeeded in gaining further insight in the functioning of endogenous mechanisms that protect against the development of Alzheimer's disease. It was found that the activity of the enzyme α-secretase is mainly responsible for the protective effect. ...

"The α-secretase enzyme is a highly complex one, with many other functions. For example, it also relays signals from the intercellular space into cells and interacts with molecules on other cells." Fahrenholz and his colleagues have now established, following investigations in a transgenic mouse model, that it is the enzymatic activity alone that guarantees the protective effects. If this activity is neutralised, the laboratory mice exhibit the symptoms that are characteristic of Alzheimer's disease: impaired learning ability, poor memory capacity and the build-up of Aβ plaques. It is thus possible that the enzymatic activity of α-secretase could represent the starting point for the development of future treatments.

At the same time, the researchers were able to confirm with their experiments that it is not the plaque build-up itself that is responsible for the loss of memory capacity. The cytotoxic substances that accumulate in plaques only destroy neuron synapses when they are still in solution. Prof. Fahrenholz concludes: "It is important to consider other aspects in addition to the plaques themselves, particularly their precursors, which are a real cause of the disease."


That is a fairly bold statement ("real cause"), but more data is pointing to at least a combination of things responsible for Alzheimer's not just the A-beta plaque.

Again, Fahrenholz is in no way saying that his results imply the irrelevance of Abeta, but that Abeta species "only destroy neuron synapses when they are still in solution" -- that "in addition to the plaques themselves, " "their precursors, which are a [not, NB, "the" -MR] real cause of the disease."
Indeed, as the press article indicates, what's happening here is that it's not some external effect of alpha-secretase that gives the enzyme its protective effect, but "the activity of the enzyme α-secretase [that] is mainly responsible for the protective effect." "The activity" is the cleavage of amyloid precursor protein (APP/betaAPP) into various physiological signaling molecules; this denies APP as a precursor to beta-secretase (BACE), so that "If this activity is neutralised, the laboratory mice exhibit the symptoms that are characteristic of Alzheimer's disease ... [including] the build-up of Aβ plaques".

It's also certainly true that when alpha-secretase's production of its normal physiological products is impaired, this in itself will have negative effects on brain structure and function, contributing to the progression of the disease; one mechanism of such denial appears to be (wait for it) the upregulation of BACE activity by aggregation-prone Abeta species (Abeta42):

HEK293 cells overexpressing wild-type betaAPP exhibit a DFK167-sensitive increase in BACE1 promoter transactivation that is increased by the Abeta-potentiating Swedish mutation. This effect was mimicked by exogenous application of Abeta42 but not Abeta40 or by transient transfection of cDNA encoding Abeta42 sequence. ... Furthermore, APP/beta-amyloid precursor protein-like protein deficiency does not affect BACE1 activity and expression. Overall, these data suggest that physiological levels of endogenous Abeta are not sufficient per se to modulate BACE1 promoter transactivation but that exacerbated Abeta production ... modulates BACE1 promoter transactivation and activity via an NFkappaB-dependent pathway. (3)


As to (b) the op cit comments of Drs. Mufson and Koliatsos: this is in my view hyperbolic at best. In particular, to say that the new study "comes at a time when amyloid, the predominant target of therapy for Alzheimer disease, has not given us great therapeutic products or solutions" is really not very helpful: Abeta removal strategies are only now getting into Phase III trials, so it's hardly reasonable to complain that they haven't delivered yet. (Cf the much more egregious -- indeed, completely disingenuous -- example of embryonic stem cells, whose less-ethical bioconservative opponents complain "haven't cured any diseases," while we have a zillion "therapies" (nearly all of which amount to bone marrow transplant) available now from adult stem cells. Of course, we only first even cultured ESCs a decade ago, and they've been under political constraints and market uncertainty almost from the first day of their derivation; indeed, the people sneering "no cures!" are the very same people pushing for restrictions on developing those cures, while the "adult stem cells" they're touting are largely haematopoietic stem cells, on which we've enjoyed forty years of unrestricted research and clinical experience.

-Michael

References
1: Han L, Zhang Z, Qin W, Sun W. Neurotrophic receptor TrkB: Is it a predictor of
poor prognosis for carcinoma patients? Med Hypotheses. 2007;68(2):407-9. Epub
2006 Sep 27. PubMed PMID: 17008023.

2. Nakagawara A, Azar CG, Scavarda NJ, Brodeur GM. Expression and function ofTRK-B and BDNF in human neuroblastomas. Mol Cell Biol. 1994 Jan;14(1):759-67.
PubMed PMID: 8264643; PubMed Central PMCID: PMC358424.

3. : Buggia-Prevot V, Sevalle J, Rossner S, Checler F. NFkappaB-dependent controlof BACE1 promoter transactivation by Abeta42. J Biol Chem. 2008 Apr
11;283(15):10037-47. Epub 2008 Feb 8. PubMed PMID: 18263584.
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#28 maestro949

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Posted 05 May 2009 - 08:12 PM

I also think that there's been some confusion on one particular point:


No confusion. Brain function was improved by targetting BDNF irrespective of deposit level. If I am predisposed to, or experiencing the affects of Alzheimers, I'd like to halt its progression and reverse its affects rather than lose my memories. If the gunk building up can be removed as well, super.

Moreover, as Aubrey regularly emphasizes, dynamic metabolic pathways like the ones regulating BDNF are 'set' where they are for a reason, and overriding those regulatory pathways inevitably carries risks; in the case of boosting BDNF, the most obvious one would be cancer, since many cancers (including, in particular, neuroblastomas in the brain) exploit the BDNF signaling pathway to help them resist apoptotic signaling and increase needed vascularization:


But of course. Any intervention carries risks. Even those that simply try to degrade aggregates. We currently have a plethora of drugs that alter various metabolic and regulatory pathways directly or indirectly today. What's a few more?

On that first bit, (a) the fact that BDNF is effective "independent of the amount of amyloid deposited" isn't evidence that Abeta isn't a major contributor to AD, or that its removal isn't central to its arrest and ultimate reversal; rather, it's again evidence for what has actually been the dominant model for much of the last decade: that the smaller, soluble oligomeric Abeta species, rather than the deposited, fibrillar plaque, is the critical Abeta species (though the plaque is unlikely to be helpful except as a dispensible 'sink'). Similarly on the alpha-secretase experiment:


With Alzheimer's, has there been any evidence that the accumulating junk is anything beyond a useful biomarker, i.e. actually impacting memory and cognition? I have yet to see any. This phase I trial cleared amyloid plaques but the progression of the disease continued!


Although immunisation with Abeta(42) resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not prevent progressive neurodegeneration.

Link: http://www.ncbi.nlm....pubmed/18640458



But I think that the idea that an agent to protect cells from the toxic effects of aging damage is ultimately superior to repairing that damage is somewhat implausible on its face: certainly, BDNF might be a good short-term, stopgap measure, but it can only reduce the damaging effects, not eliminate them, whereas removing the underlying damage removes the secondary effects of that damage gratis.


Organisms and their cells already have agents to protect themselves from toxicity for numerous decades. If there are mechanisms already in place(immune system, microglia and other macrophages, organelles, dna repair, etc) that can protect against aging and finding a means to prop them up might be a better alternative than simply trying to mop up all the "after the fact" downstream damage. This would be true particularly if numerous innate repair mechanisms are declining with time. The "ounce of prevention is worth a pound of cure" approach may be our fastest route to significant longevity. I'm all for targeting after-the-fact damage but I don't see any data yet that suggests that cleaning it up is going to have all that significant of an impact on longevity, it's just speculation at this point, as is any other theoretical approach.

As to (b) the op cit comments of Drs. Mufson and Koliatsos: this is in my view hyperbolic at best. In particular, to say that the new study "comes at a time when amyloid, the predominant target of therapy for Alzheimer disease, has not given us great therapeutic products or solutions" is really not very helpful...


I don't disagree that slamming existing efforts is helpful but I don't follow your subsequent line of reasoning. It suggests that there is only one solution to the problem and we simply need to give targeting the aggregates more time, which I am all in favor of. I'm not a fan of ruling out any proposal, particularly for diseases we still know so little about. Are you suggesting that all researchers should focus on a single strategy to deal with Alzheimer's? I wouldn't want to put all my eggs in one basket. Studying the regulatory mechanisms, metabolic changes and existent repair mechanisms could and likely will lead to a much more effective treatments.

#29 tunt01

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Posted 05 May 2009 - 08:24 PM

without discounting the value, importance, and potential role of BDNF in multiple therapies (including AD), I think Michael's point is that targeting the aggregates is a far more 'elegant' solution. Assuming this is feasible, I happen to agree.

I've been casually reading about AD for a few years now and this struck me as one of the more promising concepts for a solution to that end:

http://www.imminst.o...o...st&p=316946

I think any intelligent person would likely recognize, that both aggregate targeting and BDNF could play a role on a LT basis for comprehensive treatment.

just my 2 cents.

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#30 tunt01

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Posted 06 May 2009 - 08:23 PM

http://www.scienceda...90506144309.htm

Gene Key To Alzheimer's-like Reversal Identified: Success In Restoring Memories In Mice Could Lead To Human Treatments

ScienceDaily (May 6, 2009) — A team led by researchers at MIT's Picower Institute for Learning and Memory has now pinpointed the exact gene responsible for a 2007 breakthrough in which mice with symptoms of Alzheimer's disease regained long-term memories and the ability to learn.
See also:
Health & Medicine

In the latest development, reported in the May 7 issue of Nature, Li-Huei Tsai, Picower Professor of Neuroscience, and colleagues found that drugs that work on the gene HDAC2 reverse the effects of Alzheimer's and boost cognitive function in mice.
........
The researchers treated mice with Alzheimer's-like symptoms using histone deacetylase (HDAC) inhibitors. HDACs are a family of 11 enzymes that seem to act as master regulators of gene expression. Drugs that inhibit HDACs are in experimental stages and are not available by prescription for use for Alzheimer's.

"Harnessing the therapeutic potential of HDAC inhibitors requires knowledge of the specific HDAC family member or members linked to cognitive enhancement," Tsai said. "We have now identified HDAC2 as the most likely target of the HDAC inhibitors that facilitate synaptic plasticity and memory formation."



curcumin and resveratrol modulate HDAC2, not sure if anyone else knows HDAC2 inhibitors offhand




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