Brain Aging : Pathogenesis from the cerebral β amyloid deposition to the development of the dementia.

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To know how Alzheimer's disease develops from the cerebral β amyloid deposition, which is frequently seen in the non-demented elderly people, we have collected autopsied brains and formed the Gunma Senile Brain Bank. We have measured the amounts of deposited Aβ by ELISA as well as evaluated them by immunohistochemistry. We found that cerebral β amyloid deposition precedes the abnormal accumulation of phosphorylated tau. We also analyzed ApoE genotypes, and found that ApoE4 promotes earlier beginning of the cerebral β amyloid deposition.We further studied the ultrastructural localization of β protein in the early stage of amyloid deposition, and found that β protein starts to deposits on a part of the cell surface plasma membrane as membrane-bound Aβ. Flotillin, a marker protein of the cerebral DIG/caveolae, was found diffusely in the cerebral cortex, and the amounts of it increased according to the degree of the cerebral β amyloid deposition.We also studies the ultrastructural localization of β-amyloid-related proteins, amyloid β protein precursor(APP)and β amyloid cleaving enzyme(BACE), and found that these proteins localize to the cytoplasmic vesicles.