Mechanism of dense plaques at the Alzheimer's disease.

Amyloid-ß (Aß) aggregation in brain parenchyma as dense-core and diffuse plaques, and in vascular walls, are a major neuropathological feature of Alzheimer's disease. Dense-core plaques are considered neurotoxic. Several lines of evidence suggest that Aß does not aggregate spontaneously in brain but is rather assisted by specific chaperones that help Aß to aggregate into ß-sheets. We recently identified vessels to be a major site where dense-core plaques develop in both transgenic mouse models and patients of Alzheimer's disease, suggesting that vessels are a hot-spot for such Aß assembly-promoting factors. Interestingly, vessels free of Aß deposition have also been shown to have a number of structural microvascular abnormalities in both Alzheimer's patients and transgenic mouse models suggesting that vascular pathology is also important in the pathogenesis of Alzheimer's disease. Utilizing transcriptomic and proteomic analysis, the current project aims to elucidate the mechanism(s) of dense-core plaque formation at vascular sites as well as to understand changes that occur in these vessels prior to plaque deposition in various transgenic mouse models of Alzheimer's disease. These studies would in turn further aid in identifying novel potential therapeutic targets for preventing or treating Alzheimer's disease.

Keywords:AMYLOIDOSIS AND TAUOPATHY, ALZHEIMER'S DISEASE, ANIMAL MODELS, BLOOD VESSELS

Disciplines:Laboratory medicine, Morphological sciences, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing