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Oral Resveratrol Stabilizes Amyloid in Alzheimer's

alzheimers resveratrol

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#1 maxwatt

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Posted 02 December 2014 - 04:56 AM


Don't know if this actually stops Alzheimer's - targeting amyloid plaque has not so far produced results, but if it seems to be a marker rather than a cause, this could be promising.  It's a human trial, the dose is reasonable at 500 mg, amyloid in cerebrospinal fluid was reduced, and other markers of the disease showed improvement.

 

 

PHILADELPHIA, Pennsylvania — High-dose oral resveratrol (RES) administration stabilized levels of amyloid-beta 40 (Aβ40) in cerebrospinal fluid (CSF) and plasma compared with placebo in patients with mild to moderate Alzheimer's disease (AD), a phase 2 study shows.

"We found that oral resveratrol and its major metabolites penetrate the blood–brain barrier and seemed to have [central nervous system (CNS)] actions at nanomolar concentrations," said lead author R. Scott Turner, MD, PhD, professor of neurology and director of the Memory Disorders Program at Georgetown University in Washington, DC.

"Based on its safety and tolerability and CNS penetration and effects on biomarkers, we might consider further studies on resveratrol, or perhaps synthetic, more bioavailable compounds that mimic the actions of resveratrol," Dr Turner concluded.

The findings were reported here at the 7th Clinical Trials Conference on Alzheimer's Disease (CTAD).

 

See http://www.medscape....warticle/835614 for more information on the study.


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#2 bixbyte

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Posted 04 December 2014 - 02:54 PM

"You didn't see the change that you would normally see in Alzheimer's disease, so that is a positive signal, but again, it calls for more research," he said.

 

 

 



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#3 bixbyte

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Posted 04 December 2014 - 10:03 PM

http://www.medscape....warticle/835614

 

 

In the phase 2, double-blind, multicenter, 12-month trial, participants were randomly assigned to receive either oral RES 500 mg once daily (N = 64), escalating to 1000 mg twice daily at 13-week intervals, or matching placebo (n = 55). RES was added onto approved drugs for AD.

 

RES treatment altered Aβ40 levels in CSF and plasma and was associated with a loss of brain volume and an increase in ventricular volume, possibly explained by reduced edema and inflammation.

 

Resveratrol Well Tolerated

The major adverse effects occurring more frequently with RES were nausea (14 when receiving RES vs 5 when receiving placebo) and diarrhea (26 when receiving RES vs 7 when receiving placebo).

 

 

 

Neoplasms were more frequent in the placebo group (seven cancers in six participants: three malignant melanomas, two squamous cell carcinomas, one basal cell carcinoma, and one malignant glioma) and were rare in the RES group (one bladder cancer; P = .048 for all neoplasms in the RES group vs placebo). Other adverse events were similar between the two groups.

Eleven RES patients lost weight compared with none in the placebo group (P = .049). Most of the weight change occurred after week 26. By week 52, the RES group had lost about 1.2 kg compared with baseline, and the placebo group had gained about 1.5 kg.

 

_________________________

 

This study is incredible and My Wife and I have been supplementing with at least one gram of Resveratrol / day for about 8 years.

 

 

 

 

 


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#4 Michael

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Posted 22 December 2014 - 12:41 AM

It's important to note that while "RES treatment altered Aβ40 levels in CSF and plasma," "RES had no effect on Aβ42 in CSF or plasma, CSF tau or phospho-tau-181, hippocampal volume, or entorhinal cortex thickness, all of which were prespecified primary outcomes of the trial." In nearly all studies, CSF Aβ40 levels remain stable thru'out the leadup into and course of AD, so altering that more or less stable trajectory most likely has no prognostic or causal significance. By contrast, CSF Aβ42 levels quite consistently fall during the preclinical phase, continue to fall or remain stable during the transition from MCI to AD, and then remain stable after dementia onset. So the fact that there's no effect on Aβ42 — or on CSF tau or phospho-tau-181, hippocampal volume, or entorhinal cortex thickness, all of which are known predictors of AD dementia and were prespecified primary outcomes of the trial — is inconsistent with a protective effect of RES on AD risk or onset.

 

The fact that RES use "was associated with a loss of brain volume and an increase in ventricular [non-parenchymal, CSF-filled "empty" brain space] volume" might conceivably be "explained by reduced edema and inflammation" in the brain — there's reason to think this is what's happening with similar paradoxical findings in Abeta immunotherapy — but of course it could also be the result of increased brain atrophy.


Edited by Michael, 22 December 2014 - 12:42 AM.

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#5 bixbyte

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Posted 28 December 2014 - 01:25 AM

It's important to note that while "RES treatment altered Aβ40 levels in CSF and plasma," "RES had no effect on Aβ42 in CSF or plasma, CSF tau or phospho-tau-181, hippocampal volume, or entorhinal cortex thickness, all of which were prespecified primary outcomes of the trial." In nearly all studies, CSF Aβ40 levels remain stable thru'out the leadup into and course of AD, so altering that more or less stable trajectory most likely has no prognostic or causal significance. By contrast, CSF Aβ42 levels quite consistently fall during the preclinical phase, continue to fall or remain stable during the transition from MCI to AD, and then remain stable after dementia onset. So the fact that there's no effect on Aβ42 — or on CSF tau or phospho-tau-181, hippocampal volume, or entorhinal cortex thickness, all of which are known predictors of AD dementia and were prespecified primary outcomes of the trial — is inconsistent with a protective effect of RES on AD risk or onset.

 

The fact that RES use "was associated with a loss of brain volume and an increase in ventricular [non-parenchymal, CSF-filled "empty" brain space] volume" might conceivably be "explained by reduced edema and inflammation" in the brain — there's reason to think this is what's happening with similar paradoxical findings in Abeta immunotherapy — but of course it could also be the result of increased brain atrophy.

 

 

 

Beta Amyloids note that Aβ40 is an important marker to predisposition of A/D

 

http://en.wikipedia....ki/Amyloid_beta

 

Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are crucially involved in Alzheimer's disease as the main component of the amyloid plaques found in the brains of Alzheimer patients

...

A number of genetic, cell biology, biochemical and animal studies support the concept that Aβ plays a central role in the development of Alzheimer’s disease pathology.....

 

Brain Aβ is elevated in patients with sporadic Alzheimer’s disease. Aβ is the main constituent of brain parenchymal and vascular amyloid; it contributes to cerebrovascular lesions and is neurotoxic.[23][24][25][26] It is unresolved how Aβ accumulates in the central nervous system and subsequently initiates the disease of cells. Some researchers have found that the Aβ oligomers induce some of the symptoms of Alzheimer's Disease by competing with insulin for binding sites on the insulin receptor, thus impairing glucose metabolism in the brain.[27] Significant efforts have been focused on the mechanisms responsible for Aβ production, including the proteolytic enzymes alpha- and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein).[28][29][30][31] Aβ circulates in plasma, cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) mainly as soluble Aβ40[23][32] Senile plaques contain both Aβ40 and Aβ42,[33] while vascular amyloid is predominantly the shorter Aβ40. Several sequences of Aβ were found in both lesions.[34][35][36] Generation of Aβ in the CNS may take place in the neuronal axonal membranes after APP-mediated axonal transport of β-secretase and presenilin-1.[37]

 

..............

 

Increases in either total Aβ levels or the relative concentration of both Aβ40 and Aβ42 (where the former is more concentrated in cerebrovascular plaques and the latter in neuritic plaques)[38] have been implicated in the pathogenesis of both familial and sporadic Alzheimer's disease. 

 

 

 

 

Formation

Aβ is formed after sequential cleavage of the amyloid precursor protein (APP), a transmembrane glycoprotein of undetermined function. APP can be cleaved by the proteolytic enzymes α-, β- and γ-secretase; Aβ protein is generated by successive action of the β and γ secretases. The γ secretase, which produces the C-terminal end of the Aβ peptide, cleaves within the transmembrane region of APP and can generate a number of isoforms of 36-43 amino acid residues in length. The most common isoforms are Aβ40 and Aβ42; the longer form is typically produced by cleavage that occurs in the endoplasmic reticulum, while the shorter form is produced by cleavage in the trans-Golgi network.[41] The Aβ40 form is the more common of the two, but Aβ42 is the more fibrillogenic and is thus associated with disease states. Mutations in APP associated with early-onset Alzheimer's have been noted to increase the relative production of Aβ42, and thus one suggested avenue of Alzheimer's therapy involves modulating the activity of β and γ secretases to produce mainly Aβ40.[42] Aβ is destroyed by several amyloid-degrading enzymes including neprilysin.[43]

 

 

 

 

 

 

 

(Thus the Resveratrol had a positive effect compared to the Placebo Group in lowering their chances of acquiring Alzheimers)

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#6 Michael

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Posted 31 December 2014 - 04:56 AM

All:

 

 

It's important to note that while "RES treatment altered Aβ40 levels in CSF and plasma," "RES had no effect on Aβ42 in CSF or plasma [...]"  In nearly all studies, CSF Aβ40 levels remain stable thru'out the leadup into and course of AD, so altering that more or less stable trajectory most likely has no prognostic or causal significance. By contrast, CSF Aβ42 levels quite consistently fall during the preclinical phase, continue to fall or remain stable during the transition from MCI to AD, and then remain stable after dementia onset. So the fact that there's no effect on Aβ42 — or on CSF tau or phospho-tau-181, hippocampal volume, or entorhinal cortex thickness, all of which are known predictors of AD dementia and were prespecified primary outcomes of the trial — is inconsistent with a protective effect of RES on AD risk or onset.

 

 

Beta Amyloids note that Aβ40 is an important marker to predisposition of A/D

 

http://en.wikipedia....ki/Amyloid_beta

 

(Thus the Resveratrol had a positive effect compared to the Placebo Group in lowering their chances of acquiring Alzheimers)

 

To be clear, I agree entirely that Aβ40 is involved in AD, and more importantly in cerebral amyloid angiopathy (and through it, cogntive impairment and dementia). But that's a different question from what the implications are of RES' effect on CSF levels

of Aβ40 vs. Aβ42. As I indicated, "CSF Aβ40 levels remain stable thru'out the leadup into and course of AD, so altering that more or less stable trajectory most likely has no prognostic or causal significance. By contrast, CSF Aβ42 levels quite consistently fall during the preclinical phase, continue to fall or remain stable during the transition from MCI to AD, and then remain stable after dementia onset. So the fact that there's no effect on Aβ42 — or on CSF tau or phospho-tau-181, hippocampal volume, or entorhinal cortex thickness, all of which are known predictors of AD dementia and were prespecified primary outcomes of the trial — is inconsistent with a protective effect of RES on AD risk or onset."
 


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#7 bixbyte

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Posted 01 January 2015 - 12:25 AM

All:

 

 

It's important to note that while "RES treatment altered Aβ40 levels in CSF and plasma," "RES had no effect on Aβ42 in CSF or plasma [...]"  In nearly all studies, CSF Aβ40 levels remain stable thru'out the leadup into and course of AD, so altering that more or less stable trajectory most likely has no prognostic or causal significance. By contrast, CSF Aβ42 levels quite consistently fall during the preclinical phase, continue to fall or remain stable during the transition from MCI to AD, and then remain stable after dementia onset. So the fact that there's no effect on Aβ42 — or on CSF tau or phospho-tau-181, hippocampal volume, or entorhinal cortex thickness, all of which are known predictors of AD dementia and were prespecified primary outcomes of the trial — is inconsistent with a protective effect of RES on AD risk or onset.

 

 

Beta Amyloids note that Aβ40 is an important marker to predisposition of A/D

 

http://en.wikipedia....ki/Amyloid_beta

 

(Thus the Resveratrol had a positive effect compared to the Placebo Group in lowering their chances of acquiring Alzheimers)

 

To be clear, I agree entirely that Aβ40 is involved in AD, and more importantly in cerebral amyloid angiopathy (and through it, cogntive impairment and dementia). But that's a different question from what the implications are of RES' effect on CSF levels

of Aβ40 vs. Aβ42. As I indicated, "CSF Aβ40 levels remain stable thru'out the leadup into and course of AD, so altering that more or less stable trajectory most likely has no prognostic or causal significance. By contrast, CSF Aβ42 levels quite consistently fall during the preclinical phase, continue to fall or remain stable during the transition from MCI to AD, and then remain stable after dementia onset. So the fact that there's no effect on Aβ42 — or on CSF tau or phospho-tau-181, hippocampal volume, or entorhinal cortex thickness, all of which are known predictors of AD dementia and were prespecified primary outcomes of the trial — is inconsistent with a protective effect of RES on AD risk or onset."
 

 

There is nothing "protective" supplementing with RES for AD symptoms  ;)  but I certainly want my CSF AB40 levels reduced. 

Same response as I originally posted inflammation and edema are possibly reduced by lowered

Plaque Levels in the Brain or as they were identified in the study as Beta Amyloid 40 levels. 

On MRIs of AD patients MDs rule out hydrocephalus that are in actuality Brain edema and inflammation.

 

 

RES treatment altered Aβ40 levels in CSF and plasma and was associated with a loss of brain volume and an increase in ventricular volume, possibly explained by reduced edema and inflammation.

 


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