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

为了了解阿尔茨海默病是如何从大脑β淀粉样蛋白沉积发展而来的，这在非痴呆老年人中很常见，我们收集了尸检大脑，并建立了群马老年脑库。我们用ELISA法测定了Aβ的沉积量，并用免疫组化法对其进行了评价。我们发现大脑β淀粉样蛋白沉积先于磷酸化tau蛋白的异常积累。我们还分析了ApoE基因型，发现ApoE 4促进脑β淀粉样蛋白沉积的早期开始，进一步研究了β蛋白在淀粉样蛋白沉积早期的超微结构定位，发现β蛋白以膜结合Aβ的形式开始沉积在细胞表面的部分质膜上。Flotillin是大脑DIG/小窝的标志蛋白，在大脑皮质广泛分布，其含量随β淀粉样蛋白沉积程度的增加而增加，我们还研究了β淀粉样蛋白相关蛋白、淀粉样β蛋白前体（APP）和β淀粉样蛋白裂解酶（BACE）的超微结构定位，发现这些蛋白定位于胞浆小泡。

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.