Gene expression profiles of cholinergic nucleus basalis neurons in Alzheimer's disease

被引:119
作者
Mufson, EJ
Counts, SE
Ginsberg, SD
机构
[1] Rush Presbyterian St Lukes Med Ctr, Rush Alzheimers Dis Res Ctr, Dept Neurol Sci, Chicago, IL 60612 USA
[2] NYU, Sch Med, Dept Psychiat, Nathan Kline Inst,Ctr Dementia Res, Orangeburg, NY 10902 USA
关键词
Alzheimer's disease; cholinergic basal forebrain; cDNA microarray; RNA amplification; synaptophysin; cathepsin D;
D O I
10.1023/A:1020952704398
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cholinergic neurons of the nucleus basalis (NB) are selectively vulnerable in Alzheimer's disease (AD), yet the molecular mechanisms associated with their dysfunction remain unknown. We used single cell RNA amplification and custom array technology to examine the expression of functional classes of mRNAs found in anterior NB neurons from normal aged and AD subjects. mRNAs encoding neurotrophin receptors, synaptic proteins, protein phosphatases, and amyloid-related proteins were evaluated. We found that trkB and trkC mRNAs were selectively down-regulated in NB neurons, whereas p75(NTR) mRNA levels remained stable in end stage AD. TrkA mRNA was reduced by approximately 28%, but did not reach statistical significance. There was a down-regulation of synaptophysin, synaptotagmin, and protein phosphatases PP1alpha and PP1beta mRNAs in AD. In contrast, we found a selective up-regulation of cathepsin D mRNA in NB neurons in AD brain. Thus, anterior NB neurons undergo selective alterations in gene expression in AD. These results may provide clues to the molecular pathogenesis of NB neuronal degeneration during AD.
引用
收藏
页码:1035 / 1048
页数:14
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