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

Document Type

Article

Abstract

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 p75NTR 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 PP1α and PP1β 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.

Keywords

Alzheimer's disease, Cathepsin D, CDNA microarray, Cholinergic basal forebrain, RNA amplification, Synaptophysin

Publication Date

1-1-2002

Publication Title

Neurochemical Research

ISSN

03643190

Volume

27

Issue

10

First Page

1035

Last Page

1048

PubMed ID

12462403

Digital Object Identifier (DOI)

10.1023/A:1020952704398

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