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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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References

Arai, H., Noguchi, I., Saigi, N., Moroji, T. & Izizuka, R. (1989). A study of non-isotopic in situ hybridization histochemistry on post mortem changes in vasopressin mRNA in rat brain. Neuroscience Letters 103, 127132.CrossRefGoogle Scholar
Ball, M. J. (1978). Topographic distribution of neurofibrillary tangles and granulovacuolar degeneration in hippocampal cortex of aging and demented patients. A quantitative study. Acta Neuropathologica (Berlin) 42, 7380.CrossRefGoogle ScholarPubMed
Ball, M. J., Hachinski, V., Fox, A., Kirshen, A. J., Fisman, M., Blume, W., Kral, V. A., Fox, H. & Merskey, H. (1985). A new definition of Alzheimer's disease: a hippocampal dementia. Lancet i, 1416.CrossRefGoogle Scholar
Barton, A. J. L. & Hardy, J. A. (1987). Stability of brain RNA post mortem: effect of Alzheimer's disease. Biochemical Society Transactions 15, 558559.CrossRefGoogle Scholar
Barton, A. J. L., Harrison, P. J., Najlerahim, A., Heffernan, J., McDonald, B., Robinson, J. R., Davies, D. C., Harrison, W. J., Mitra, P., Hardy, J. A. & Pearson, R. C. A. (1990). Increased tau messenger RNA in Alzheimer's disease hippocampus. American Journal of Pathology 137, 497502.Google ScholarPubMed
Beach, T. G. & McGeer, E. G. (1988). Lamina-specific arrangement of astrocytic gliosis and senile plaques in Alzheimer disease visual cortex. Brain Research 463, 357361.CrossRefGoogle ScholarPubMed
Bernstein, P. & Ross, J. (1989). Poly(A), poly (A) binding protein and the regulation of mRNA stability. Trends in Biochemical Sciences 14, 373377.CrossRefGoogle Scholar
Braak, H., Braak, E., Bohl, J. & Lang, W. (1989). Alzheimer's disease: amyloid plaques in the cerebellum. Journal of Neurological Science 93, 277287.CrossRefGoogle ScholarPubMed
Bustany, P., Henry, J. F., Sargent, T., Zorifian, E., Cabanis, E., Collard, P. & Comar, D. (1983). Local brain protein metabolism in dementia and schizophrenia: in vivo studies with [11C]L-methionine and positron emission tomography. In Positron Emission Tomography of the Brain (ed. Heiss, W. D. and Phelps, M. E.), pp. 208211. Springer: New York.CrossRefGoogle Scholar
Chaudhari, N. & Hahn, W. E. (1983). Genetic expression in the developing brain. Science 220, 924928.CrossRefGoogle ScholarPubMed
Clark, A. W. & Parhad, I. M. (1989). Expression of neuronal mRNAs in Alzheimer type degeneration of the nervous system. Canadian Journal of the Neurological Sciences 16, 477482.CrossRefGoogle ScholarPubMed
Coleman, P. D. & Flood, D. G. (1987). Neuron numbers and dendritic extent in normal aging and Alzheimer's disease. Neurobiology of Aging 8, 521545.CrossRefGoogle ScholarPubMed
Cowburn, R. F., Hardy, J. A. & Roberts, P. J. (1989). Neurotransmitter deficits in Alzheimer's disease. In Alzheimer's Disease: Towards an Understanding of the Aetiology and Pathogenesis (ed. Davies, D. C.), pp. 932. John Libbey: London.Google Scholar
Crapper McLachlan, D. R. & Lewis, P. N. (1985). Alzheimer's disease: errors in gene expression. Canadian Journal of the Neurological Sciences 12, 15.CrossRefGoogle Scholar
Crapper McLachlan, D. R., Lukiw, W. J., Wong, L., Bergeron, C. & Bech-Hansen, N. T. (1988). Selective messenger RNA reduction in Alzheimer's disease. Molecular Brain Research 3, 255262.CrossRefGoogle Scholar
Davies, D. C. (1989). Hippocampal pathology and memory impairment in Alzheimer's disease. In Alzheimer's Disease: Towards an Understanding of the Aetiology and Pathogenesis (ed. Davies, D. C.), pp. 89105. John Libbey: London.Google Scholar
Davis, L. G., Dibner, M. D. & Batty, J. F. (1986). Basic Methods in Molecular Biology. Elsevier: New York.Google Scholar
Doebler, J. A., Markesbery, W. R., Anthony, A. & Rhoads, R. E. (1987). Neuronal RNA in relation to neuronal loss and neurofibrillary pathology in the hippocampus in Alzheimer's disease. Journal of Neuropathology and Experimental Neurology 46, 2839.CrossRefGoogle ScholarPubMed
Doebler, J. A., Markesbery, W. R., Anthony, A., Scheff, S. W. & Rhoads, R. E. (1988). Astrocyte RNA in relation to neuronal RNA depletion in Alzheimer's disease. Acta Neuropathologica (Berlin) 75, 272276.CrossRefGoogle ScholarPubMed
Doebler, J. A., Rhoads, R. E., Anthony, A. & Markesbery, W. R. (1989). Neuronal RNA in Pick's and Alzheimer's diseases: comparison of disease-susceptible and disease-resistant cortical areas. Archives of Neurology, 46, 134137.CrossRefGoogle ScholarPubMed
Duvernoy, H. M. (1988). The Human Hippocampus. J. F. Bergman: Munich.CrossRefGoogle Scholar
Finch, C. E. & Morgan, D. G. (1990). RNA and protein metabolism in the aging brain. Annual Review of Neuroscience 13, 7587.CrossRefGoogle ScholarPubMed
Geddes, J. W., Wong, J., Choi, B. H., Kim, R. C., Cotman, C. W. & Miller, F. D. (1990). Increased expression of the embryonic form of a developmentally-regulated mRNA in Alzheimer's disease. Neuroscience Letters 109, 5461.CrossRefGoogle ScholarPubMed
Griffin, W. S. T., Ling, C., White, C. L. & Morrison-Bogorad, M. (1990). Polyadenylated messenger RNA in paired helical filament- immunoreactive neurons in Alzheimer disease. Alzheimer Disease and Associated Disorders 4, 6978.CrossRefGoogle ScholarPubMed
Guillemette, J. G., Wong, L., Crapper McLachlan, D. R. & Lewis, P. N. (1986). Characterization of messenger RNA from the cerebral cortex of control and Alzheimer-afflicted brain. Journal of Neurochemistry 47, 987997.CrossRefGoogle ScholarPubMed
Harrison, P. J. & Pearson, R. C. A. (1989). Gene expression and mental disease. Psychological Medicine 19, 813819.CrossRefGoogle ScholarPubMed
Harrison, P. J. & Pearson, R. C. A. (1990). In situ hybridization histochemistry and the study of gene expression in the human brain. Progress in Neurobiology 34, 271312.CrossRefGoogle Scholar
Harrison, P. J., Barton, A. J. L., Najlerahim, A. & Pearson, R. C. A. (1990). Distribution of a kainate/AMPA receptor mRNA in normal and Alzheimer brain. Neuro Report 1, 149152.Google ScholarPubMed
Harrison, P. J., Barton, A. J. L., Najlerahim, A., McDonald, B. & Pearson, R. C. A. (1991 a). Increased muscarinic receptor messenger RNA in Alzheimer's disease temporal cortex demonstrated by in situ hybridization histochemistry. Molecular Brain Research 9, 1521.CrossRefGoogle ScholarPubMed
Harrison, P. J., Barton, A. J. L., McDonald, B. & Pearson, R. C. A. (1991 b). Alzheimer's disease: specific increases in a G protein subunit (G,α) mRNA in hippocampal and cortical neurons. Molecular Brain Research 10, 7181.CrossRefGoogle Scholar
Harrison, P. J., Procter, A. W., Barton, A. J. L., Lowe, S. L., Najlerahim, A., Bertolucci, P. H. F., Bowen, D. M. & Pearson, R. C. A. (1991 c). Terminal coma affects messenger RNA detection in post mortem human temporal cortex. Molecular Brain Research 9, 161164.CrossRefGoogle ScholarPubMed
Hof, P. R., Bouras, C., Constantinidis, J. & Morrison, J. H. (1989). Selective dissociation of specific visual association pathways in cases of Alzheimer's disease presenting with Balint's syndrome. Journal of Neuropathology and Experimental Neurology 49, 168184.CrossRefGoogle Scholar
Jackson, R. J. & Standard, N. (1990). Do the poly(A) tail and 3′ untranslated region control mRNA translation? Cell 62, 1524.CrossRefGoogle ScholarPubMed
Joachim, C. L., Morris, J. H. & Selkoe, D. J. (1989). Diffuse senile plaques occur commonly in the cerebellum in Alzheimer's disease. American Journal of Pathology 135, 309319.Google ScholarPubMed
Johnson, S. A., Morgan, D. G. & Finch, C. E. (1986). Extensive post-mortem stability of mRNA from rat and human brain. Journal of Neuroscience Research 16, 267280.CrossRefGoogle Scholar
Jones, L. M. & Knowler, J. T. (1989). Role of ribonuclease and ribonuclease inhibitor activities in Alzheimer's disease. Journal of Neurochemistry 53, 13411344.CrossRefGoogle ScholarPubMed
Khachaturian, Z. S. (1985). Diagnosis of Alzheimer's disease. Archives of Neurology 42, 10971105.CrossRefGoogle ScholarPubMed
Kosik, K. S., Crandall, J. E., Mufson, E. J. & Neve, R. L. (1989). Tau in situ hybridization in Alzheimer brain: localization in the somatodendritic compartment. Annals of Neurology 26, 352361.CrossRefGoogle ScholarPubMed
Langstrom, N. S., Anderson, J. P., Lindroos, H. G., Winblad, B. & Wallace, W. C. (1989). Alzheimer's disease-associated reduction of polysomal mRNA translation. Molecular Brain Research 5, 259269.CrossRefGoogle ScholarPubMed
Lewis, D. A., Campbell, M. J., Terry, R. D. & Morrison, J. H. (1987). Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices. Journal of Neuroscience 7, 17991808.CrossRefGoogle ScholarPubMed
Mann, D. M. A. & Sinclair, K. G. A. (1978). The quantitative assessment of lipofuscin pigment, cytoplasmic RNA and nucleolar volume in senile dementia. Neuropathology and Applied Neurobiology 4, 129135.CrossRefGoogle ScholarPubMed
Mann, D. M. A., Neary, D., Yates, P. O., Lincoln, J., Snowden, J. S. & Stanworth, P. (1981). Alterations in protein synthetic capability of nerve cells in Alzheimer's disease. Journal of Neurology, Neurosurgery and Psychiatry 44, 97102.CrossRefGoogle ScholarPubMed
Man, D. M. A., Yates, P. O. & Marcyniuk, B. (1985). Some morphometric observations on the cerebral cortex and hippocampus in presenile Alzheimer's disease, senile dementia of the Alzheimer type and Down's syndrome in middle age. Journal of Neurological Science 69, 139159.CrossRefGoogle Scholar
Marotta, C. A., Majocha, R. E., Coughlin, J. F., Manz, H. J., Davies, P., Ventosa-Michelman, M., Chou, W.-G., Zain, S. B. & Sajdel-Sulkowska, E. M. (1986). Transcriptional and translational regulatory mechanisms during normal aging of the mammalian brain and in Alzheimer's disease. Progress in Brain Research 70, 303320.CrossRefGoogle ScholarPubMed
Maschoff, K., White, C. L. II, Jennings, L. W. & Morrison-Bogorad, M. R. (1989). Ribonuclease activities and distribution in Alzheimer's and control brains. Journal of Neurochemistry 52, 10711078.CrossRefGoogle Scholar
May, P. C., Johnson, S. A., Poirier, J., Lampert-Etchells, M. & Finch, C. E. (1989). Altered gene expression in Alzheimer's disease brain tissue. Canadian Journal of the Neurological Sciences 16, 473476.CrossRefGoogle ScholarPubMed
Mengod, G., Charli, J.-L. & Palacios, J. M. (1990). The use of in situ hybridization histochemistry for the study of neuropeptide gene expression in the human brain. Cellular and Molecular Neurobiology 10, 113126.CrossRefGoogle Scholar
Morrison, M. R., Pardue, S., Maschoff, K., Griffin, W. S. T., White, C. L., Gilbert, J. & Roses, A. (1987). Brain messenger RNA levels and ribonuclease activity in Alzheimer's disease. Biochemical Society Transactions 15, 133134.CrossRefGoogle ScholarPubMed
Naber, D. & Dahnke, H. G. (1979). Protein and nucleic acid content in the aging human brain. Neuropathology and Applied Neurobiology 5, 1724.CrossRefGoogle ScholarPubMed
Netsky, M. G. (1968). Degenerations of the cerebellum and its pathways. In Pathology of the Nervous System, (ed. Minckler, J.), pp. 11631185. McGraw Hill: New York.Google Scholar
Neve, R. L. (1990). Genetics of the Alzheimer amyloid precursor. In Molecular Aspects of Development and Aging of the Nervous System (ed. Lauder, J. M.), pp. 291299. Plenum Press: New York.CrossRefGoogle Scholar
Pearson, R. C. A. & Powell, T. P. S. (1989). The neuroanatomy of Alzheimer's disease. Reviews in the Neurosciences 2, 101122.CrossRefGoogle ScholarPubMed
Pearson, R. C. A., Esiri, M. M., Hiorns, R. W., Wilcock, G. & Powell, T. P. S. (1985). Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer's disease. Proceedings of the National Academy of Sciences, USA 82, 45314535.CrossRefGoogle Scholar
Perrett, C. W., Marchbanks, R. M. & Whatley, S. A. (1988). Characterisation of messenger RNA extracted post-mortem from the brains of schizophrenic, depressed and control subjects. Journal of Neurology, Neurosurgery and Psychiatry 51, 325331.CrossRefGoogle ScholarPubMed
Ross, J. (1989). The turnover of messenger RNA. Scientific American 260, 2835.CrossRefGoogle ScholarPubMed
St George Hyslop, P. H., Haines, J. L., Farrer, L. A., Polinsky, R., Van Broeckhoven, C., Goate, A., Crapper McLachlan, D. R., Orr, H., Bruni, A. C., Sorbi, S., Rainero, I., Foncin, J.-F., Pollen, D., Cantu, J.-M., Tupler, R., Voskresenskaya, N., Mayeux, R., Growdon, J., Fried, V. A., Myers, R. H., Nee, L., Backhovens, H., Martin, J.-J., Rossor, M. N., Owen, M. J., Mullan, M., Percy, M. E., Karlinsky, H., Rich, S., Heston, L., Montesi, M., Mortilla, M., Nacmias, N., Gusella, J. F. & Hardy, J. A. (1990). Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. Nature 347, 194197.CrossRefGoogle Scholar
Sajdel-Sulkowska, E. M. & Marotta, C. A. (1984). Alzheimer's disease brain: alterations in RNA levels and in a ribonuclease-inhibitor complex. Science 225, 947949.CrossRefGoogle Scholar
Sajdel-Sulkowska, E. M., Majocha, R. A., Salim, M., Zain, S. B. & Marotta, C. A. (1988). The post mortem Alzheimer brain is a source of structurally and functionally intact astrocytic messenger RNA. Journal of Neuroscience Methods 23, 173179.CrossRefGoogle Scholar
Selkoe, D. J. (1989). Biochemistry of altered brain proteins in Alzheimer's disease. Annual Review of Neuroscience 12, 463490.CrossRefGoogle ScholarPubMed
Somerville, M. J., Percy, M. E., Bergeron, C., Yoong, L. K. K., Grima, E. A. & McLachlan, D. R. C. (1991). Localization and quantitation of 68 kDa neurofilament and superoxide dismutase-I mRNA in Alzheimer brain. Molecular Brain Research 9, 114.CrossRefGoogle Scholar
Tabaton, M., Cammarata, S., Manetto, V., Perry, G. & Mancardi, G. (1989). Tau-reactive neurofibrillary tangles in cerebellar cortex from patients with Alzheimer's disease. Neuroscience Letters 103, 259262.CrossRefGoogle ScholarPubMed
Taylor, G. R., Carter, G. I., Crow, T. J., Johnson, J. A., Fairbairn, A. F., Perry, E. K. & Perry, R. H. (1986). Recovery and measurement of specific RNA species from postmortem brain tissue: a general reduction in Alzheimer's disease detected by molecular hybridization. Experimental and Molecular Pathology 44, 111116.CrossRefGoogle Scholar
Tomlinson, B. E. & Corsellis, J. A. N. (1984). Aging and the dementias. In Greenfield's Neuropathology, 4th edn. (ed. Adams, J. H., Corsellis, J. A. N. and Duchen, L. W.), pp. 9511025. Butterworth: London.Google Scholar
Uemura, E. & Hartmann, H. (1979). Quantitative studies of neuronal RNA on the subiculum of demented old individuals. Brain Research Bulletin 4, 301305.CrossRefGoogle ScholarPubMed
Walker, D. G., Boyes, P. L. & McGeer, E. G. (1989). Strategies for the identification of novel brain specific genes affected in Alzheimer's disease. Canadian Journal of Neurological Sciences 16, 483489.CrossRefGoogle Scholar
Zhang, H., Sternberger, N. H., Rubinstein, L. J., Herman, M. M., Binder, L. I. & Sternberger, L. A. (1989). Abnormal phosphorylation of multiple proteins in Alzheimer's disease. Proceedings of the National Academy of Sciences USA 86, 80458049.CrossRefGoogle Scholar