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Altered Gene Expression in Alzheimer's Disease Brain Tissue

Published online by Cambridge University Press:  18 September 2015

Patrick C. May*
Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles
Steven A. Johnson
Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles
Judes Poirier
Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles
Martha Lampert-Etchells
Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles
Caleb E. Finch
Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles
Andrus Gerontology Center, University of Southern California, Los Angeles, CA, U.S.A. 90089-0191
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We review the evidence for altered gene expression in Alzheimer's disease brain and identify alternative molecular approaches for isolating additional novel markers. One marker, pADHC-9, was isolated from a human hippocampal cDNA library by differential screening with AD and control cDNA probes. This clone hybridizes to a 2 Kb RNA which is increased 2 fold in AD hippocampus. The deduced amino acid sequence of pADHC-9 codes for a 52 kDAL protein similar to a testicular sulfated glycoprotein secreted by rat Sertoli cells. The normal function of this protein in brain and whether that function is altered in Alzheimer's disease is unknown.

Research Article
Copyright © Canadian Neurological Sciences Federation 1989



1.Ball, MJ, Hachinski, V, Fox, A, et al. A new definition of Alzheimer’s disease: a hippocampal dementia. Lancet 1985; 1: 1416.CrossRefGoogle ScholarPubMed
2.Hyman, BT, Van Hoesen, GW, Damasio, AR, et al. Cell specific pathology isolates the hippocampal formation. Science 1984; 225: 11681170.CrossRefGoogle ScholarPubMed
3.Hyman, BT, Van Hoesen, GW, Kramer, LJ, et al. Perforant pathway changes and the memory impairment of Alzheimer’s disease. Ann Neurol 1986; 20: 472481.CrossRefGoogle ScholarPubMed
4.Geddes, JW, Monaghan, DT, Cotman, CW, et al. Plasticity of hippocampal circuitry in Alzheimer’s disease. Science 1985; 230: 11791181.CrossRefGoogle ScholarPubMed
5.Hyman, BT, Kramer, U, Van Hoesen, GW. Reinnervation of the hippocampal perforant pathway zone in Alzheimer’s disease. Ann Neurol 1987; 21: 259267.CrossRefGoogle ScholarPubMed
6.Probst, A, Basler, V, Bron, B, et al. Neuritic plaques in senile dementia of Alzheimer type: a Golgi analysis in the hippocampal region. Brain Res 1983; 268: 249254.CrossRefGoogle ScholarPubMed
7.Cotman, CW, Nieto-Sampedro, M. Reactive synaptogenesis in the hippocampus. Science 1985; 225: 12871294.CrossRefGoogle Scholar
8.Sajdel-Sulkowska, EM, Maratta, CA. Alzheimer’s disease brain alterations in RNA levels and a ribonuclease-inhibitor complex. Science 1984; 225: 947949.CrossRefGoogle Scholar
9.Taylor, GR, Carter, GI, Crow, TJ, et al. Measurement of relative con-centrations of RNA in postmortem brains from senile dementia of the Alzheimer type (SDAT) and controls. J Neurogenet 1985; 2: 177.Google Scholar
10.Guillemette, JG, Wong, L, Crapper-McLachlan, DR, et al. Characterization of messenger RNA from the cerebral cortex of control and Alzheimer-afflicted brain. J Neurochem 1986; 47: 987997.CrossRefGoogle ScholarPubMed
11.May, PC, Johnson, SA, Masters, JN, et al. Cloning of poly(A)RNA differentially regulated in Alzheimer’s disease from a hippocampal cDNA library. Soc Neurosci Abs 1987; 13: 1325.Google Scholar
12.Wallace, W, Winblad, B. Progress towards a molecular genetic approach to Alzheimer’s disease. Neuro-psychopharmacol Biol Psychiat 1986; 10: 657663.CrossRefGoogle Scholar
13.Johnson, SA, Morgan, DG, Finch, CE. Extensive postmortem stability of RNA from rat and human brain. J Neurosci Res 1986; 16: 272280.CrossRefGoogle ScholarPubMed
14.Morrison, MR, Pardue, S, Maschoff, K, et al. Brain messenger RNA and ribonuclease activity in Alzheimer’s disease. Biochem Soc Trans 1986; 15: 133134.CrossRefGoogle Scholar
15.Doebler, JA, Markesbery, WR, Anthony, A, et al. Neuronal RNA in relation to Alz-50 immunoreactivity in Alzheimer’s disease. Ann Neurol 1988; 23: 2024.CrossRefGoogle ScholarPubMed
16.Mann, DMA. The neuropathology of Alzheimer’s disease: a review with pathogenetic, aetiological and therapeutic considerations. Mech Ageing Devel 1985; 31: 213255.CrossRefGoogle ScholarPubMed
17.Mann, DMA, Neary, D, Yates, PO, et al. Neurofibrillary pathology and protein synthetic capability in nerve cells in Alzheimer’s disease. Neuropathol Appi Neurobiol 1981; 7: 3747.CrossRefGoogle ScholarPubMed
18.Mann, DMA, Neary, D, Yates, PO, et al. Alterations in protein synthetic capability in nerve cells in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1981; 44: 97102.CrossRefGoogle ScholarPubMed
19.Wolozin, BL, Pruchnicki, A, Dickson, DW, et al. A neuronal antigen in the brains of Alzheimer patients. Science 1986; 232: 648652.CrossRefGoogle ScholarPubMed
20.Hyman, BT, Van Hoesen, GW, Wolozin, BL, et al. Alz-50 antibody recognizes Alzheimer-related neuronal changes. Ann Neurol 1988; 23: 371379.CrossRefGoogle ScholarPubMed
21.Doebler, JA, Markesbery, WR, Anthony, A, et al. Neuronal RNA in relation to neuronal loss and neurofibrillary degeneration in Alzheimer diseased hippocampus. J Neuropath Exp Neurol 1987; 466: 2829.CrossRefGoogle Scholar
22.Wolozin, BL, Scicutella, A, Davies, P. Reexpression of a developmentally regulated antigen in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 1988; 85: 62026206.CrossRefGoogle ScholarPubMed
23.Bahmanyar, S, Higgins, GA, Goldgaber, D, et al. Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer’s disease. Science 1987; 237: 7780.CrossRefGoogle ScholarPubMed
24.Higgins, GA, Lewis, DA, Young, WG, et al. Differential regulation of amyloid-6-protein mRNA expression within hippocampal neuronal subpopulations in Alzheimer disease. Proc Natl Acad Sci USA 1988; 85: 12971301.CrossRefGoogle ScholarPubMed
25.Kitaguchi, N, Takahashi, Y, Tokushima, Y, et al. Novel precursor of Alzheimer’s disease amyloid A4 protein shows protease inhibitory activity. Nature 1988; 331: 530532.CrossRefGoogle Scholar
26.Ponte, P, Gonzalez-DeWhitt, J, Schilling, J, et al. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature 1988; 331: 525527.CrossRefGoogle ScholarPubMed
27.Tanzi, RE, McClatchey, AI, Lamperti, EG, et al. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer’s disease. Nature 1988; 331: 528530.CrossRefGoogle ScholarPubMed
28.Cohen, ML, Golde, TE, Usiak, MF, et al. In situ hybridization of nucleus basalis neurons shows increased B-amyloid mRNA in Alzheimer disease. Proc Natl Acad Sci USA 1988; 85: 12271232.CrossRefGoogle Scholar
29.Lewis, DA, Higgins, GA, Young, WG, et al. Distribution of precursor amyloid-B-messenger RNA in human cerebral cortex. Proc Natl Acad Sci USA 1988; 85: 16911695.CrossRefGoogle ScholarPubMed
30.Abraham, CR, Selkoe, DL, Potter, H. Immunochemical identification of the serine protease inhibitor alpha- 1-antichymotrypsin in the brain amyloid deposits of Alzheimer’s disease. Cell 1988; 52: 487501.CrossRefGoogle ScholarPubMed
31.Zain, SZ, Salim, M, Chou, W-G, et al. Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer Disease brain: coding and noncoding regions of the fetal mRNA are expressed in the cortex. Proc Natl Acad Sci USA 1988; 85: 929933.CrossRefGoogle ScholarPubMed
32.Salim, M, Rehman, S, Sajdel-Sukowska, EM, et al. Preparation of a recombinant cDNA library from poly(A+)RNA of the Alzheimer brain. Identification and characterization of a cDNA copy encoding a glial-specific protein. Neurobiol Aging 1988; 9: 163171.CrossRefGoogle ScholarPubMed
33.Dammerman, M, Goldstein, M, Yen, S-HC, et al. Isolation and characterization of cDNA clones encoding epitopes shared with Alzheimer neurofibrillary tangles. J Neurosci Res 1988; 19: 4351.CrossRefGoogle Scholar
34.Goedert, M, Wischik, CM, Crowther, RA, et al. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci USA 1988; 85:40514055.CrossRefGoogle ScholarPubMed
35.Miller, CA, Rudnicka, M, Hinton, DR, et al. Monoclonal antibody identification of subpopulations of cerebral cortical neurons affected in Alzheimer disease. Proc Natl Acad Sci USA 1987; 84: 86578661.CrossRefGoogle ScholarPubMed
36.May, PC, Johnson, SA, Lampert-Etchells, MA, et al. In situ mapping of pADHC-9: a poly(A)RNA sequence overexpressed in Alzheimer’s disease hippocampus. Soc Neurosci Abs 1988; 14: 897.Google Scholar
37.May, PC, Lampert-Etchells, MA, Anderson, CP, et al. The Alzheimer’s related hippocampal cDNA clone pADHC-9 encodes a 52 kDAL protein similar to a rat testicular sulfated glycoprotein. Soc Neurosci Abs (in press).Google Scholar
38.Collard, MW, Griswold, MD. Biosynthesis and molecular cloning of sulfated glycoprotein 2 secreted by rat sertoli cells. Biochemistry 1987; 26: 32973303.CrossRefGoogle ScholarPubMed
39.Poirier, J, May, PC, Finch, CE. Alteration in glial fibrillary acidic protein mRNA content in the rat hippocampus after entorhinal cortex lesion. Soc Neurosci Abs 1987; 14: 897.Google Scholar
40.Weidemann, A, Konig, G, Bunke, D. Identification, biogenesis and localization of precursors of Alzheimer’s disease A4 amyloid protein. Cell 1989; 57: 115126.CrossRefGoogle ScholarPubMed
41.Johnson, SA, Rogers, J and Finch, CE. APP-695 transcript prevalence is selectively reduced during Alzheimer’s disease in cortex, hippocampus but not in cerebellum. Neurobiol Aging 1989; 10: 267272.CrossRefGoogle ScholarPubMed