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Regional and neuronal reductions of polyadenylated messenger RNA in Alzheimer's disease

Published online by Cambridge University Press:  09 July 2009

Paul J. Harrison*
Affiliation:
Departments of Anatomy and Psychiatry, St Mary's Hospital Medical School, London; Department of Biomedical Science, The University, Sheffield; Department of Neuropathology, Radcliffe Infirmary, Oxford
Amanda J. L. Barton
Affiliation:
Departments of Anatomy and Psychiatry, St Mary's Hospital Medical School, London; Department of Biomedical Science, The University, Sheffield; Department of Neuropathology, Radcliffe Infirmary, Oxford
Abdolrahman Najlerahim
Affiliation:
Departments of Anatomy and Psychiatry, St Mary's Hospital Medical School, London; Department of Biomedical Science, The University, Sheffield; Department of Neuropathology, Radcliffe Infirmary, Oxford
Brendan McDonald
Affiliation:
Departments of Anatomy and Psychiatry, St Mary's Hospital Medical School, London; Department of Biomedical Science, The University, Sheffield; Department of Neuropathology, Radcliffe Infirmary, Oxford
*
1Address for correspondence: Dr P. J. Harrison, University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX.

Synopsis

Messenger RNA (mRNA) is the key intermediate in the gene expression pathway. The amount of mRNA in Alzheimer's disease (AD) brains has been determined using in situ hybridization histochemistry (ISHH) to detect the poly(A) tails of polyadenylated mRNA (poly(A) + mRNA). On a regional basis, AD cases had significantly less poly(A) + mRNA than controls in hippocampus (field CA3) and cerebellum (granule cell layer). Analysis of constituent pyramidal neurons showed mean reductions per cell within AD hippocampus (field CA3) and temporal cortex, but not in visual cortex. Similar changes were seen in a small group of non-AD dementias. The finding of reduced poly(A) + mRNA content is another indication of the altered brain gene expression occurring in AD. It is proposed that measurement of poly(A) + mRNA may be valuable in identifying functionally impaired neuronal populations. The methodology also provides a means by which changes in the quantitative distribution of individual mRNAs can be determined relative to that of poly(A) + mRNA as a whole.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 1991

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