The entry of molecular genetics into the field of Alzheimer's disease in the last few years has led to the usual plethora of data that results when any new methodology is applied to an old problem. The information has been of both a positive and negative type. On the positive side, the genes for two components of the Alzheimer amyloid deposits (the β–protein and the protease inhibitor α1–antichymotrypsin) have been identified, one previously unsuspected, and at least some families harboring the inherited form of Alzheimer's disease have been shown to carry their autosomal dominant mutation on chromosome 21. On the negative side, the early hoped–for explanation of familial Alzheimer's disease as a mutation in the β–protein or a triplication of the β–protein gene turned out not to be forthcoming, and the potential heterogeneity of familial Alzheimer's disease indicated by some studies means we still have much genetic work to do. The molecular genetic studies have also provided potential insights into the biochemistry of amyloid formation and into the normal function of the β–protein precursor.
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Terry, R.D., Hansen, L.A., DeTeresa, R., Davies, P., Tobias, H. et al. 1987. Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles. J. Neuropathol. Exp. Neurol. 46:262–268.
Abraham, C.R., Selkoe, D.J., and Potter, H. 1988. Immunochemical identification of the serine protease inhibitor arantichymotrypsin in the brain amyloid deposits of Alzheimer's disease. Cell 52:487–501.
Wisniewski, H.M., Rabe, A., and Wisniewski, K.E. 1988. Neuropathology and dementia in people with Down's syndrome, p. 399–413. In: Molecular Neuropathology of Aging. Banbury Report. P. Davies, C. Finch (Eds.). New York: Cold Spring Harbor Laboratory.
Selkoe, D.J., Ihara, Y., and Salazar, F.J. (1982). Alzheimer's disease: insolubility of partially purified helical filaments in sodium dodecyl sulfate and urea. Science 115:1243–1245.
Ihara, Y., Abraham, C.R., and Selkoe, D.J. 1983. Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins. Nature 304:727–730.
Glenner, G.G. and Wong, C.W. 1984. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovas-cular amyloid protein. Biochem. Biophys. Res. Commun. 122:885–890.
Masters, C.L., Multhaup, G., Simms, G., Pottgieser, J., Martins, R.N., and Beyreuther, K. 1985. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J. 4:2757.
Wong, C.W., Quaranta, V., and Glenner, G.G. 1985. Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are anti-genically related. Proc. Nat. Acad. Sci. USA 82:8729–8732.
Selkoe, D.J., Abraham, C.R., Podlisny, M.B., and Duffy, L.K. 1986. Isolation of low-molecular weight proteins from amyloid plaque fibers in Alzheimer's disease. J. Neurochem. 46:1820–1834.
Goldgaber, D., Lerman, M.J., McBride, O.W., Safnotti, V., and Gadjusek, D.C. 1987. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science 235:877.
Kang, J., Lemaire, H.G., Unterback, A., Salbaum, J.M., Masters, C.L., Grezeschik, K.H., Multhaup, G., Beyreuther, K., and Muller-Hill, B. 1987. The precursor of Alzheimer disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733.
Tanzi, R.E., Gusella, J.F., Watkins, P.C., Bruns, G.A.P., St. George-Hyslop, P., Van Keuren, M.L., Patterson, D., Pajan, S., Kurnit, D.M., and Neve, R.L. 1987. Amyloid β-protein gene; cDNA, mRNA distributions, and genetic linkage near the Alzheimer locus. Science 235:880.
Robakis, N.K., Ramakrishna, N., Wolfe, G., and Wisniewski, H.M. 1987. Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc. Natl. Acad. Sci. USA 84:4190.
Selkoe, D.J., Podlisny, M.B., Joachim, C.L., Vickers, E.A., Lee, G., Fritz, L.C., and Oltersdorf, T. 1988. β-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kiloDalton membrane-associated proteins in neural and nonneural tissues. Proc. Natl. Acad. Sci. USA 85:7341–7345.
Tabaton, M., Morandi, A., Masters, C., Beyreuther, K., Perry, G., Gambetti, P., and Autilio-Gambetti, L. 1988. Immunoreactivity of fibroblasts from Alzheimer, Down and control cases with an antiserum to amyloid (A4) synthetic peptide. J. Neuropathol. Exp. Neurol. 47:336.
Palmert, M.R., Podlisny, M.B., Witker, D.S., Oltersdorf, T., Younkin, L.H., Selkoe, D.J., and Younkin, S.G. 1988. Antisera to an aminoterminal peptide detect the amyloid protein precursor of Alzheimer's disease and recognize senile plaques. Biochem. Biophys. Res. Comm. 156:432–437.
Palmert, M.R., Podlisny, M.B., Witker, D.S., Oltersdorf, T., Younkin, L.H., Schenk, D.B., Selkoe, D.J., and Younkin, S.G. 1988. The β amyloid protein precursor has soluble derivatives that are present in the cerebrospinal fluid of patients with Alzheimer's disease. Submitted for publication.
Card, J.P., Meade, R.P., and Davis, L.G. 1988. Immunocytochemical localization of the precursor protein for β-amyloid in the rat central nervous system. Neuron 1:835–846.
Weidemann, A., König, G., Bunke, D., Fischer, P., Master, C.L., and Beyreuther, K. 1989. Identification, biogenesis and localization of precursors of Alzheimer's disease A4 amyloid protein. Submitted.
Dyrks, T., Weidemann, A., Multhaup, G., Salbaum, J.M., Lemaire, H.-G., Kang, J., Muller-Hill, B., Masters, C.L., and Beyreuther, K. 1988. Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease. EMBO J. 7:949–957.
Goedert, M. 1987. Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer's disease. EMBO J. 6:3627–3632.
Bahmanyar, S., Higgins, G.A., Goldgaber, D., Lewis, D.A., Morrison, J.H., Wilson, M.C., Shankar, S.K., and Gajdusek, D.C. 1987. Localization of amyloid 3 protein messenger RNA in brains from patients with Alzheimer's disease. Science 237:77–80.
Cohen, M.L., Golde, T.E., Usiak, M.F., Younkin, L.H., and Younkin, S.G. 1988. In situ hybridization of nucleus basalis neurons shows increased p-amyloid mRNA in Alzheimer disease. Proc. Natl. Acad. Sci. USA 85:1227–1231.
Higgins, G.A., Lewis, D.A., Bahmanyar, S., Goldgaber, D., Gajdusek, D.C., Young, W.G., Morrison, J.H., and Wilson, M.C. 1988. Differential regulation of amyloid- β-protein mRNA expression within hippocampal neuronal subpopulations in Alzheimer disease. Proc. Natl. Acad. Sci. USA 85:1297–1301.
Ponte, P., Gonzalez-DeWhitt, P., Schilling, J., Miller, J., Hsu, D., Greenberg, B., Davis, K., Wallace, W., Lieberburg, I., Fuller, F., and Cordell, B. 1988. A new A4 amyloid mRNA contains a domain homologous to serine protease inhibitors. Nature 331:525–527.
Tanzi, R.E., McClatchey, A.I., Lamberti, E.D., Villa-Komaroff, L., Gusella, J.F., and Neve, R.L. 1988. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature 331:528–530.
Kitaguchi, N., Takahashi, Y., Tokushima, Y., Shiojiri, S., and Ito, H. 1988. Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature 331:530–532.
Palmert, M.R., Golde, T.E., Cohen, M.L., Kovacs, D.M., Tanzi, R.E., Gusella, J.F., Usiak, M.F., Younkin, L.H., and Younkin, S.G. 1988. Amyloid protein precursor messenger RNAs: differential expression in Alzheimer's disease. Science 241:1080–1084.
Neve, R.L., Finch, E.A., and Dawes, L.R. 1988. Expression of the Alzheimer amyloid precursor gene transcripts in the human brain. Neuron 1:669–677.
Johnson, S.A., Paginetti, G.M., and Finch, C.E. 1988. Reduction of APP-695 beta amyloid transcript prevalence in Alzheimer disease cortex. Soc. Neurosci. Abstr. 14:895.
Schubert, D., Schroeder, R., LaCorbiere, M., Saitoh, T., and Cole, G. 1988. Amyloid β protein precursor is possibly a heparan sulfate proteoglycan core protein. Science 241:223–226.
Wisniewski, H.M. and Terry, R. D. 1973. Morphology of the aging brain, human and animal, p. 1108–1109. In: Progress in Brain Research, Vol. 40, Neurobiological Aspects of Maturation and Aging. D. H. Ford (Ed.). Amsterdam: Elsevier.
Struble, R.G., Price, D.L. Jr., Cork, L.C. and Price, D.L. 1985. Senile plaques in cortex of aged normal monkeys. Brain Res. 361:267–275.
Selkoe, D.J., Bell, D.S., Podlisny, M.B., Price, D.L., and Cork, L.C. 1987. Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease. Science 235:873–877.
Abraham, C.R., Selkoe, D.J., Potter, H., Price, D.L., and Cork, L.C. 1988. α1-antichymotrypsin: age-related co-localization with the β-protein in monkey brain amyloid deposits. Submitted for publication.
Mandybur, T.I. 1975. The incidence of cerebral amyloid angiopathy in Alzheimer's disease. Neurology 25:120–126.
Tomonoga, M. 1981. Cerebral amyloid angiopathy in the elderly. J. Amer. Geriatr. Soc. 29:151–157.
Joachim, C.L., Duffy, L.K., Morris, J., and Selkoe, D.J. 1988. Protein chemical and immunocytochemical studies of meningovascular β-amyloid protein in Alzheimer's disease and normal aging. Brain Res., in press.
Justice, D.L., Rhodes, R.H., and Tokes, Z.A. 1987. Immunohis-tochemical demonstration of proteinase inhibitor α1-antichymotrypsin in normal human central nervous system. J. Cell. Biochem. 34:227–238.
Feldman, R.G., Chandler, K.A., Levy, L., and Glaser, G.H. 1963. Familial Alzheimer's disease. Neurology 13:811–824.
Heston, L.L., Mastri, A.R., Anderson, V.E., and White, J. 1981. Dementia of the Alzheimer type. Clinical genetics, natural history, and associated conditions. Arch. Gen. Psychiat. 38:1084–1090.
Matsuyama, S.S., Jarvik, L.F. and Kumar, V. 1985. Dementia: genetics, In: Recent Advances in Psychogeriatries. T. Arie (Ed,). Edinburgh, Churchill-Livingstone.
Jarvik, L.F. and Matsuyama, S.S. 1986. Dementia of the Alzheimer type: genetic aspects, p. 17–20. In: The Biological Substrates of Alzheimer's Disease. A. B. Scheibel and A. F. Wechslev (Eds.). Orlando, Florida: Academic Press.
Terry, R.D. 1978. Aging, senile dementia and Alzheimer's disease. Aging 7 11–14.
Terry, R.D. 1978. Ultrastructural alterations in senile dementia. Aging 7:377–382.
McKahnn, G., Drachman, D., Folstein, M., Katzman, R., and Price, D. 1984. Clinical diagnosis of Alzheimer's disease. Neurology 34:939–944.
St George-Hyslop, P.H., Tanzi, R.E., Polinsky, R.J., Raines, J.L., Nee, L. et al. 1987. The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science 235:885–889.
Jervis, G.A. 1948. Early senile dementia in mongoloid idiocy. Am J. Psychiat. 105:102–106.
Burger, P.C. and Vogel, F.S. 1973. The development of the pathological changes of Alzheimer's disease and senile dementia in patients with Down's syndrome. Am. J. Pathol. 73:457–476.
Whalley, L.J. and Buckton, K.E. 1979. Genetic factors in Alzheimer's disease, p. 36–41. In: Alzheimer's Disease: Early Recognition of Potentially Reversible Deficits. A. I. M. Glen, L.J. Whalley (Eds.). Edinburgh: Churchill-Livingstone.
Tanzi, R.E., St George-Hyslop, P.H., Haines, J.L., Polinsky, R.J., Nee, L., Foncin, J.-F., Neve, R.L., McClatchey, A.I., Conneally, P.N., and Gusella, J.F. 1987. The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid β-protein gene. Nature 329:156–157.
Korenberg, J.R. West, R., and Pulst, S.-M. 1988. The Alzheimer protein precursor gene maps to chromosome 21 sub-bands q21.15-q21.2. Neurology 38(Suppl.1):265.
Van Broekhoven, C., Genthe, A.M., Vandenberghe, A., Horsthemke, B., Backhovens, H., et al. 1987. Failure of familial Alzheimer's disease to segregate with the A4-amyloid gene in several European families. Nature 329:153–155.
Schellenberg, G.D., Bird, T.D., Wijsman, E.M., Moore, D.K., Boehnke, M., Bryant, E.M., Lampe, T.H., Nochlin, D., Sumi, S.M., Deep, S.S., Beyreuther, K., and Martin, G.M. 1988. Absence of linkage of chromosome 21q21 markers to familial Alzheimer's disease. Science 241:1507–1510.
Travis, J. and Salvesen, G.S. 1983. Human plasma proteinase inhibitors. Ann. Rev. Biochem. 52:655–709.
Pittman, R.N. 1984. Neuron-target cell interactions may involve protease-inhibitor interactions. Soc. Neurosci. Abstr. 10:662.
Pittman, R.N. 1985. Release of plasminogen activator and a calcium-dependent metalloprotease from cultured sympathetic and sensory neurons. Dev. Biol. 110:91–101.
Krystosek, A. and Seeds, N.W. 1984. Peripheral neurons and Schwann cells secrete plasminogen activator. J. Cell. Biol. 98:773–776.
Pittman, R.N. and Patterson, P.H. 1987. Characterization of an inhibitor of neuronal plasminogen activator released by heart cells. J. Neurosci. 7:2664–2673.
Kalderon, N. 1984. Schwann cell proliferation and localized proteolysis: expression of plasminogen-activator activity predominates in the proliferating cell populations. Proc. Natl. Acad. Sci. USA 81:7216–7220.
Monard, D., Niday, E., Limat, A., and Solomon, F. 1983. Inhibition of protease activity can lead to neurite extension in neuroblastoma cells. Prog. Brain Res. 58:359–364.
Guenther, J., Nick, H., and Monard, D. 1985. A glia-derived neurite-promoting factor with protease inhibitory activity. EMBO J. 4:1963–1966.
Gloor, S., Odink, K., Guenther, J., Nick, H., and Monard, D. 1986. A glia-derived neurite-promoting factor with protease inhibitory activity belongs to the protease nexins. Cell 47:687–693.
Probst, A., Basler, V., Bron, B., and Ulrich, J. 1983. Neuritic plaques in senile dementia of Alzheimer type: a Golgi analysis in the hippo-campal region. Brian Res. 268:249–254.
Geddes, J.W., Monaghan, D.T., Cotman, C.W., Lott, I.T., Kim, R.C., and Chui, H.C. 1985. Plasticity of hippocampal circuitry in Alzheimer's disease. Science 230:1179–1181.
Travis, J., Bowen, J., and Baugh, R. 1978. Human α1-antichymotrypsin: interaction with chymotrypsin-like proteinases. Biochemistry 17:5651–5656.
Castano, E.M. and Frangione, B. 1988. Biology of disease: Human amyloidosis, Alzheimer disease and related disorders. Lab. Invest. 58:122–132.
Abraham, C.R., Shiraham, T. and Potter, H. (1989). The protease inhibitor α1-antichymotrypsin is associated solely with amyloid deposits containing the β-protein and is localized in specific cells of both normal and diseased brain. Submitted for publication.
Picken, M.M., Coria, F., Larrondo-Lillo, M., Gallow, G.R., Shelanski, M.L. and Frangione, B. (1989). Distribution of the protease inhibitor arantichymotrypsin in cerebral and systematic amyloid. Submitted for publication.
Baumann, H., Jahreis, G.P., Sauder, D.N. and Koj, A. (1984). Human keratinocytes and monocytes release factors which regulate the synthesis of major acute-phase plasma proteins in hepatic cells from man, rat and mouse. J. Biol. Chem. 259:7331.
Baumann, H., Richards, C. and Gauldie, J. (1987). Interaction among hepatocyte-stimulating factors, interleukin 1, and glucocorticoids for regulation of acute phase plasma proteins in human hepatoma (HepG2) cells. J. Immunol. 139:4122–4128.
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Abraham, C., Potter, H. Alzheimer's Disease: Recent Advances in Understanding the Brain Amyloid Deposits. Nat Biotechnol 7, 147–153 (1989). https://doi.org/10.1038/nbt0289-147
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