期刊
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
卷 74, 期 4, 页码 345-358出版社
OXFORD UNIV PRESS INC
DOI: 10.1097/NEN.0000000000000179
关键词
Alzheimer disease; Autophagy; Cathepsin D; Endosomallysosomal proteins; Hippocampus; Mild cognitive impairment; mTOR; Rabaptin5
资金
- NIA [PO1AG14449, RO1AG043375, P30AG010161, RO1AG042210, PO1AG025204, PO1AG107617]
- Alzheimer's Association
- Brinson Foundation
Endosomal-lysosomal and autophagic dysregulation occurs in the hippocampus in prodromal Alzheimer disease (AD), but its relationship with A-amyloid (AA) and tau pathology remains unclear. To investigate this issue, we performed immunoblot analysis of hippocampal homogenates from cases with an antemortem clinical diagnosis of no cognitive impairment, mild cognitive impairment (MCI), and AD. Western blot analysis revealed significant increases in the acid hydrolase cathepsin D and early endosome marker rabaptin5 in the MCI group compared with AD, whereas levels of phosphorylated mammalian target of rapamycin proteins (pmTOR), total mammalian target of rapamycin (mTOR), p62, traf6, and LilrB2 were comparable across clinical groups. Hippocampal A beta 1 (40) and A beta(1) (42) concentrations and AT8-immunopositive neurofibrillary tangle density were not significantly different across the clinical groups. Greater cathepsin D expression was associated with global cognitive score and episodic memory score but not with mini mental state examination or advanced neuropathology criteria. These results indicate that alterations in hippocampal endosomal-lysosomal proteins in MCI are independent of tau or AA pathology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据