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Expression profiles of multiple genes in single neurons of Alzheimer's disease.

Abstract：

:Many changes have been described in the brains of Alzheimer's disease (AD) patients, including loss of neurons and formation of senile plaques and neurofibrillary tangles. The molecular mechanisms underlying these pathologies are unclear. Northern blot, dot-blot, and reverse transcription-coupled PCR analyses have demonstrated altered expression levels of multiple messages in AD brain. Because not all cells are equally affected by the disease, these methods obviously cannot study the changes in relation to disease states of individual cells. We address this problem by using antisense RNA profiling of single cells. We present expression profiles of single neurons at early and late stages of AD and describe statistical tools for data analysis. With multivariate canonical analysis, we were able to distinguish the disease state on the basis of altered expression of multiple messages. To validate this approach, we compared results obtained by this approach with results obtained by in situ hybridization analysis. When the neurofilament medium subunit was used as a marker, our results from an antisense RNA profiling revealed no change in neurofilament medium subunit expression between early- and late-stage AD, consistent with findings obtained with in situ hybridization. However, our results obtained by either analysis at the single-cell level differed from the reported decrease in AD neocortex obtained by Northern blot analysis [Kittur, S., Hoh, J., Endo, H., Tourtellotte, W., Weeks, B. S., Markesbery, W. & Adler, W. (1994) J. Geriatr. Psychiatry Neurol. 7, 153-158]. Thus, the strategy of using the single-cell antisense RNA approach to identify altered gene expression in postmortem AD brain, followed by detailed in situ hybridization studies for genes of interest, is valuable in the study of the molecular mechanisms underlying AD neuropathology.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Chow N,Cox C,Callahan LM,Weimer JM,Guo L,Coleman PD

doi

10.1073/pnas.95.16.9620

subject

Has Abstract

pub_date

1998-08-04 00:00:00

pages

9620-5

issue

eissn

0027-8424

issn

1091-6490

journal_volume

pub_type

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Expression profiles of multiple genes in single neurons of Alzheimer's disease.