Abstract
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.
Highlights
Alzheimer’s disease (AD) is a progressive, irreversible brain disorder with an unclear etiology and no cure
Inhibition of toxic Ab oligomer species and fibrils formation CEppt was initially tested for its ability to inhibit Ab42 oligomer formation using the protocol established by Barghorn and coworkers, which results in the formation of SDS stable offpathway oligomers [10]
CEppt fraction was precipitated from the cinnamon extract by KCl
Summary
Alzheimer’s disease (AD) is a progressive, irreversible brain disorder with an unclear etiology and no cure. Confusion, impaired judgment, disorientation, and loss of language skills [1]. Recent debate has focused on whether Ab amyloid fibrils or Ab soluble oligomers are the main neurotoxic species which contribute to neurodegeneration and dementia. Considerable evidence has indicated that amyloid fibrils are toxic [1]. Recent studies support the notion that it is the early soluble oligomers that are the primary neurotoxic agents [3,4,5,6,7,8,9]. 56 kDa (56*) dodecameric oligomers of Ab were shown to correlated with the deterioration of cognitive functions in AD model mice and their reintroduction into normal brains resulted in memory impairment [7,10]
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