AN AGE-RELATED AXON TERMINAL PATHOLOGY AROUND THE FIRST OLFACTORY RELAY THAT INVOLVES AMYLOIDOGENIC PROTEIN OVEREXPRESSION WITHOUT PLAQUE FORMATION
AN AGE-RELATED AXON TERMINAL PATHOLOGY AROUND THE FIRST OLFACTORY RELAY THAT INVOLVES AMYLOIDOGENIC PROTEIN OVEREXPRESSION WITHOUT PLAQUE FORMATION
复制标题
第一嗅觉传递周围与年龄相关的轴突末端病理，涉及淀粉样蛋白过度表达但无斑块形成
DOI：
10.1016/j.neuroscience.2012.04.043
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发表时间：
2012-07-26
期刊：
影响因子：
3.3
通讯作者：
Yan, X. -X.
中科院分区：
文献类型：
--
作者：
Cai, Y.;Xue, Z. -Q.;Yan, X. -X.
The glomeruli are the first synaptic relay on the olfactory pathway and play a basic role in smell perception. Glomerular degeneration occurs in humans with age and in Alzheimer's disease (AD). The glomeruli heavily express beta-amyloid precursor protein (APP), beta-secretase (BACE1) and gamma-secretase complex. However, extracellular beta-amyloid peptide (A beta) deposition occurs fairly rarely at this location in postmortem pathological studies. We sought to explore age-related glomerular changes that might link to alteration in amyloidogenic proteins and/or plaque pathogenesis in transgenic models of AD and humans. Focally increased BACE1 immunoreactivity (IR) in the glomerular layer was identified in several transgenic models, and characterized systematically in transgenic mice harboring five familiar AD-related mutations (5XFAD). These elements were co-labeled with antibodies against APP N-terminal (22C11) and A beta N-terminal (3D6, 6E10) and mid-sequence (4G8). They were not co-labeled with two A beta C-terminal antibodies (Ter40, Ter42), nor associated with extracellular amyloidosis. These profiles were further characterized to be most likely abnormal olfactory nerve terminals. Reduced glomerular area was detected in 6-12-month-old 5XFAD mice relative to non-transgenic controls, and in aged humans relative to young/adult controls, more robust in AD than aged subjects without cerebral amyloid and tau pathologies. The results suggest that olfactory nerve terminals may undergo age-related dystrophic and degenerative changes in AD model mice and humans, which are associated with increased labeling for amyloidogenic proteins but not local extracellular A beta deposition. The identified axon terminal pathology might affect neuronal signal transmission and integration at the first olfactory synaptic relay. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
