Curcumin may also be effective in preventing and breaking down the amyloid plaques that are associated with AD. As the following articles elucidate:
The development of preventives and therapeutics for Alzheimer's disease that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta.
* Ono K,
* Naiki H,
* Yamada M.
Department of Neurology & Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Neuritic plaques composed mainly of amyloid beta-protein (Abeta) in the brain are an early and invariant neuropathological feature of Alzheimer's disease (AD). The current search for anti-AD drugs is mainly focused on modification of the process of Abeta deposition in the brain. In this article, the recent development of the molecules that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta is reviewed. Recently, various compounds such as curcumin, nicotine and wine-related polyphenols have been reported to inhibit the formation, extension of fAbeta, as well as destabilize preformed fAbeta at pH 7.5 at 37 degrees C in vitro. In cell culture experiments, destabilized fAbeta were suggested to be less toxic than intact fAbeta. In transgenic mice model study, some coumpounds such as curcumin and nicotine have also been reported to reduce plaque burden in vivo. Although the mechanisms by which these compounds inhibit fAbeta formation from Abeta, and destabilize preformed fAbeta are still unclear, they could be key molecules for the development of preventives and therapeutics for AD.
PMID: [PubMed - in process]
1: J Alzheimers Dis. 2006 Sep;10(1):1-7.Click here to read Links
Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients.
* Zhang L,
* Fiala M,
* Cashman J,
* Sayre J,
* Espinosa A,
* Mahanian M,
* Zaghi J,
* Badmaev V,
* Graves MC,
* Bernard G,
* Rosenthal M.
Department of Medicine, Greater LA VA Medical Center and UCLA School of Medicine, Los Angeles, CA 90095, USA.
Treatment of Alzheimer's disease (AD) is difficult due to ignorance of its pathogenesis. AD patients have defects in phagocytosis of amyloid-beta (1-42) (Abeta) in vitro by the innate immune cells, monocyte/macrophages and in clearance of Abeta plaques [5]. The natural product curcuminoids enhanced brain clearance of Abeta in animal models. We, therefore, treated macrophages of six AD patients and 3 controls by curcuminoids in vitro and measured Abeta uptake using fluorescence and confocal microscopy. At baseline, the intensity of Abeta uptake by AD macrophages was significantly lower in comparison to control macrophages and involved surface binding but no intracellular uptake. After treatment of macrophages with curcuminoids, Abeta uptake by macrophages of three of the six AD patients was significantly (P<0.001 to 0.081) increased. Confocal microscopy of AD macrophages responsive to curcuminoids showed surface binding in untreated macrophages but co-localization with phalloidin in an intracellular compartment after treatment. Immunomodulation of the innate immune system by curcuminoids might be a safe approach to immune clearance of amyloidosis in AD brain.
PMID: [PubMed - indexed for MEDLINE]
1: J Biol Chem. 2005 Feb 18;280(7):5892-901. Epub 2004 Dec 7.Click here to read Links
Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo.
* Yang F,
* Lim GP,
* Begum AN,
* Ubeda OJ,
* Simmons MR,
* Ambegaokar SS,
* Chen PP,
* Kayed R,
* Glabe CG,
* Frautschy SA,
* Cole GM.
Department of Medicine, UCLA, Los Angeles, CA 90095, USA.
Alzheimer's disease (AD) involves amyloid beta (Abeta) accumulation, oxidative damage, and inflammation, and risk is reduced with increased antioxidant and anti-inflammatory consumption. The phenolic yellow curry pigment curcumin has potent anti-inflammatory and antioxidant activities and can suppress oxidative damage, inflammation, cognitive deficits, and amyloid accumulation. Since the molecular structure of curcumin suggested potential Abeta binding, we investigated whether its efficacy in AD models could be explained by effects on Abeta aggregation. Under aggregating conditions in vitro, curcumin inhibited aggregation (IC(50) = 0.8 microM) as well as disaggregated fibrillar Abeta40 (IC(50) = 1 microM), indicating favorable stoichiometry for inhibition. Curcumin was a better Abeta40 aggregation inhibitor than ibuprofen and naproxen, and prevented Abeta42 oligomer formation and toxicity between 0.1 and 1.0 microM. Under EM, curcumin decreased dose dependently Abeta fibril formation beginning with 0.125 microM. The effects of curcumin did not depend on Abeta sequence but on fibril-related conformation. AD and Tg2576 mice brain sections incubated with curcumin revealed preferential labeling of amyloid plaques. In vivo studies showed that curcumin injected peripherally into aged Tg mice crossed the blood-brain barrier and bound plaques. When fed to aged Tg2576 mice with advanced amyloid accumulation, curcumin labeled plaques and reduced amyloid levels and plaque burden. Hence, curcumin directly binds small beta-amyloid species to block aggregation and fibril formation in vitro and in vivo. These data suggest that low dose curcumin effectively disaggregates Abeta as well as prevents fibril and oligomer formation, supporting the rationale for curcumin use in clinical trials preventing or treating AD.
PMID: [PubMed - indexed for MEDLINE]
1: J Neurosci. 2001 Nov 1;21(21):8370-7.Click here to read Links
The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse.
* Lim GP,
* Chu T,
* Yang F,
* Beech W,
* Frautschy SA,
* Cole GM.
Departments of Medicine and Neurology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Inflammation in Alzheimer's disease (AD) patients is characterized by increased cytokines and activated microglia. Epidemiological studies suggest reduced AD risk associates with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed inflammation and plaque-related pathology in an Alzheimer transgenic APPSw mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase I can cause gastrointestinal, liver, and renal toxicity. One alternative NSAID is curcumin, derived from the curry spice turmeric. Curcumin has an extensive history as a food additive and herbal medicine in India and is also a potent polyphenolic antioxidant. To evaluate whether it could affect Alzheimer-like pathology in the APPSw mice, we tested a low (160 ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation, oxidative damage, and plaque pathology. Low and high doses of curcumin significantly lowered oxidized proteins and interleukin-1beta, a proinflammatory cytokine elevated in the brains of these mice. With low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP was reduced, and insoluble beta-amyloid (Abeta), soluble Abeta, and plaque burden were significantly decreased by 43-50%. However, levels of amyloid precursor (APP) in the membrane fraction were not reduced. Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease.
PMID: [PubMed - indexed for MEDLINE]
There is a lot of support for using curcumin in the treatment and perhaps the prevention of AD. Personally, as well as other here on this site consume curcumin in different ways. For my own reasons, I consume curcumin w/ bioperine to increase its bioavailability as the following article shows:
1: Planta Med. 1998 May;64(4):353-6. Links
Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.
* Shoba G,
* Joy D,
* Joseph T,
* Majeed M,
* Rajendran R,
* Srinivas PS.
Department of Pharmacology, St. John's Medical College, Bangalore, India.
The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.
PMID: [PubMed - indexed for MEDLINE]
Either curcumin or turmeric extract would be a good addition for the fight against AD. Just be cautious if you are to incorporate piperine into the mix. [thumb]
