PLoS One 2011 Jan 28;6(1):e16564. Epub 2011 Jan 28.

Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel.

An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ) play a key role in Alzheimer's disease (AD) pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt), which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet.

Neurobiol Dis 2012 Jun 19;46(3):663-72. Epub 2012 Mar 19.

Dept Molecular Microbiology & Biotechnology, Tel-Aviv University, Israel.

An increasing body of evidence indicates a role for oligomers of the amyloid-β peptide (Aβ) in the neurotoxicity of this peptide and the pathology of Alzheimer's disease (AD). Several neurotoxic oligomeric forms of Aβ have been noted ranging from the larger Amyloid β-Derived Diffusible Ligands (ADDLs) to smaller trimers and dimers of Aβ. More recently a dodecameric form of Aβ with a 56 kDa molecular weight, denoted Aβ*56, was shown to cause memory impairment in AD model mice. Read More

J Biol Chem 2012 Feb 4;287(9):6912-27. Epub 2012 Jan 4.

Department of Biomedical Sciences, Saitama Medical Center and University, Kawagoe, Saitama 350-8550, Japan.

Amyloid precursor protein (APP) proteolysis is essential for production of amyloid-β (Aβ) peptides that form β-amyloid plaques in brains of Alzheimer disease (AD) patients. Recent focus has been directed toward a group of naturally occurring anti-amyloidogenic polyphenols known as flavonoids. We orally administered the flavonoid tannic acid (TA) to the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) and evaluated cognitive function and AD-like pathology. Read More

J Neurosci 2010 Jun;30(24):8180-9

Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been demonstrated to have neuroprotective effects on ischemic, vascular dementia, and amyloid-beta (Abeta)-infused animal models. In the current study, we examined the effects of L-NBP on learning and memory in a triple-transgenic AD mouse model (3xTg-AD) that develops both plaques and tangles with aging, as well as cognitive deficits. Read More

Mol Neurobiol 2013 Dec 15;48(3):931-40. Epub 2013 Jun 15.

Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA,

Accumulation of beta-amyloid (Aβ) is an important pathological event in Alzheimer's disease (AD). It is now well known that vaccination against fibrillar Aβ prevents amyloid accumulation and preserves cognitive function in transgenic mouse models. To study the effect of vaccination against generic oligomer epitopes, Aβ oligomers, islet amyloid polypeptide oligomers, random peptide oligomer (3A), and Aβ fibrils were used to vaccinate 3xTg-AD, which develop a progressive accumulation of plaques and cognitive impairment. Read More