Shift in the ratio of three-repeat tau and four-repeat tau mRNAs in individual cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease

Document Type

Article

Abstract

Molecular mechanisms underlying tauopathy remain undetermined. In the current study, single cell gene expression profiling was coupled with custom-designed cDNA array analysis to evaluate tau expression and other cytoskeletal elements within individual neuronal populations in patients with no cognitive impairment (NCI), mild cognitive impairment (MCI), and Alzheimer's disease (AD). Results revealed a shift in the ratio of three-repeat tau (3Rtau) to four-repeat tau (4Rtau) mRNAs within individual human cholinergic basal forebrain (CBF) neurons within nucleus basalis (NB) and CA1 hippocampal neurons during the progression of AD, but not during normal aging. A shift in 3Rtau to 4Rtau may precipitate a cascade of events in the selective vulnerability of neurons, ultimately leading to frank neurofibrillary tangle (NFT) formation in tauopathies including AD. © 2006 The Authors.

Keywords

Expression profile, Microarray, Mild cognitive impairment, Neurodegeneration, Nucleus basalis, RNA amplification

Publication Date

3-1-2006

Publication Title

Journal of Neurochemistry

ISSN

00223042

E-ISSN

14714159

Volume

96

Issue

5

First Page

1401

Last Page

1408

PubMed ID

16478530

Digital Object Identifier (DOI)

10.1111/j.1471-4159.2005.03641.x

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