Reduction of cortical TrkA but not p75NTR protein in early-stage Alzheimer's disease
Reduction of cortical TrkA but not p75NTR protein in early-stage Alzheimer's disease
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DOI：
10.1002/ana.20233
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发表时间：
2004-10-01
影响因子：
11.2
通讯作者：
Mufson, EJ
中科院分区：
文献类型：
--
作者：
Counts, SE;Nadeem, M;Mufson, EJ
胆碱能基底核（NB）皮质投射神经元的变性与晚期阿尔茨海默病（AD）的认知功能下降有关。NB神经元的存活依赖于神经生长因子（NGF）受体P75（NTR）和TrkA的共表达，它们在皮质投射部位结合NGF。我们先前已经显示在AD的早期阶段，表达p75（NTR）和TrkA蛋白的NB胞体显著减少。在AD的进展过程中，这些受体的皮质水平是否伴随降低尚不清楚。p75（NTR）和TrkA蛋白通过定量免疫印迹在临床诊断为无认知损害（NCI）、轻度认知损害（MCI）、轻度/中度AD或重度AD的个体的五个皮质区域（前扣带回、上级额叶、上级颞叶、下顶叶和视觉皮质）中进行评估。皮质p75（NTR）水平在诊断组间稳定。相比之下，与NCI和MCI相比，轻度/中度和重度AD中除视觉皮层外的所有区域中的TrkA水平均降低约50%。简易精神状态检查评分与前扣带回、上级额叶和上级颞叶皮层的TrkA水平相关。皮质TrkA水平相对于p75（NTR）的选择性降低可能对从MCI向AD过渡期间的胆碱能NB功能具有重要影响。
Degeneration of cholinergic nucleus basalis (NB) cortical projection neurons is associated with cognitive decline in late-stage Alzheimer's disease (AD). NB neuron survival is dependent on coexpression of the nerve growth factor (NGF) receptors P75(NTR) and TrkA, which bind NGF in cortical projection sites. We have shown previously a significant reduction of NB perikarya expressing p75(NTR) and TrkA protein during the early stages of AD. Whether there is a concomitant reduction in cortical levels of these receptors during the progression of AD is unknown. p75(NTR) and TrkA protein was evaluated by quantitative immunoblotting in five cortical regions (anterior cingulate, superior frontal, superior temporal, inferior parietal, and visual cortex) of individuals clinically diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD, or severe AD. Cortical p75(NTR) levels were stable across the diagnostic groups. In contrast, TrkA levels were reduced approximately 50% in mild/moderate and severe AD compared with NCI and MCI in all regions except visual cortex. Mini-Mental Status Examination scores correlated with TrkA levels in anterior cingulate, superior frontal, and superior temporal cortex. The selective reduction of cortical TrkA levels relative to p75(NTR) may have important consequences for cholinergic NB function during the transition from MCI to AD.