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Animal Models of Alzheimer’s Disease

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Animal Models of Neurological Disease, I

Part of the book series: Neuromethods ((NM,volume 21))

Abstract

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a complex array of neuropathological, biochemical, and behavioral sequelae (Folstein and Whitehouse, 1983). AD is a recognized socioeconomic problem that has significant effects on a large percentage of an increasingly more aged population. Numerous experimental studies have been designed to investigate its etiology and possible pharmacotherapies for its treatment. Experimental animal models of AD are designed to reproduce a subset of the neuropathological, biochemical, and behavioral changes that have been identified in the brains of patients with AD. These animal models are, of course, inadequate because they do not completely reproduce all of the pathological and biochemical changes associated with AD; however, each model has been useful for the investigation of specific aspects of the disease. This chapter will outline the many experimental animal models of AD and compare the advantages and disadvantages of specific methodological approaches.

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References

  • Aigner T. G., Mitchell S. J., Aggleton J. P., DeLong M. R., Struble R. G., Price D. L., Wenk G. L., and Mishkin M. (1987) Effects of scopolamine and physostigmine on recognition memory in monkeys with ibotenic-acid lesions of the nucleus basalis of Meynert. Psychopharmacology 92, 292–300.

    Article  PubMed  CAS  Google Scholar 

  • Allen Y. S., Marchbanks R. M., and Sinden J. D. (1988) Non-specific effects of the putative cholinergic neurotoxin ethylcholine mustard aziridinium ion in the rat brain examined by autoradiography, immunocytochemistry and gel electrophoresis. Neurosci. Lett. 95, 69–74.

    Article  PubMed  CAS  Google Scholar 

  • Arendash G. W., Millard W. J., Dunn A. J., and Meyer E. M. (1987) Long-term neuropathological and neurochemical effects of nucleus basalis lesions in the rat. Science 238, 952–956.

    Article  PubMed  CAS  Google Scholar 

  • Arendt T., Bigl V., Tennstedt A., and Arendt A. (1985) Neuronal loss in different parts of the nucleus basalis is related to neuritic plaque formation in cortical target areas in Alzheimer’s disease. Neuroscience 14, 1–14.

    Article  PubMed  CAS  Google Scholar 

  • Atack J. R., Wenk G. L., Wagster M. V., Kellar K. J., Whitehouse P. J., and Rapoport S. I. (1989) Bilateral changes in neocortical [3H]pirenzepine and [3H]oxotremorine-M binding following unilateral lesions of the rat nucleus basalis magnocellularis: an autoradiographic study. Brain Res. 483, 367–372.

    Article  PubMed  CAS  Google Scholar 

  • Bartus R. T., Dean R. L., Beer B., and Lippa A. S. (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217, 408–417.

    Article  PubMed  CAS  Google Scholar 

  • Bartus R. T., Fleming D., and Johnson H. R. (1978) Aging in the rhesus monkey: debilitating effects on short-term memory. J. Gerontol. 33, 858–871.

    Article  PubMed  CAS  Google Scholar 

  • Bartus R. T., Flicker C., Dean, R. L., Pontecorvo M., Figuerdo J. C., and Fisher S. K. (1985) Selective memory loss following nucleus basalis lesions: long term behavioral recovery despite persistent cholinergic deficiencies. Pharmacol. Biochem. Behav. 23, 125–135.

    Article  PubMed  CAS  Google Scholar 

  • Beal M. F., Mazurek M. F., Ellison D. W., Kowall N. W., Soloman P. R., and Pendlebury W. W. (1989) Neurochemical characteristics of aluminum-induced neurofibrillary degeneration in rabbits. Neuroscience 2, 329–337.

    Google Scholar 

  • Beninger R. J., Jhamandas K., Boegman R. J., and El-Defrawy S. R. (1986) Effects of scopolamine and unilateral lesions of the basal forebrain on T-maze spatial discrimination and alternation in rats. Pharmacol. Biochem. Behav 24, 1353–1360.

    Article  PubMed  CAS  Google Scholar 

  • Bertholf R. L. (1987) Aluminum and Alzheimer’s disease: Perspectives for a cytoskeletal mechanism. CRC Crit. Rev. Clin. Lab. Sci. 25, 195–210.

    Article  CAS  Google Scholar 

  • Blessed G., Tomlinson B. E., and Roth M. (1968) The association between quantitative measures of dementia and of senile change in the grey matter of elderly subjects. Br. J. Psychiat. 114, 797–811.

    Article  CAS  Google Scholar 

  • Borson S., Barnes R. F., Veith R. C., Halter J. B., and Rasking M. A. (1989) Impaired sympathetic nervous system response to cognitive effort in early Alzheimer’s disease. J. Gerontol., 44, M8–12.

    Article  PubMed  CAS  Google Scholar 

  • Bowen D. M., Spillane J. A., Curzon G., Meier-Ruge W., White P., Goodhardt M. J., Iwangoff P., and Davison A. N. (1979) Accelerated ageing or selective neuronal loss as an important cause of dementia? Lancet 1, 11–14.

    PubMed  CAS  Google Scholar 

  • Broks P., Preston G. C., Traub M., Poppleton P., Ward C., and Stahl S. M. (1988) Modelling dementia: effects of scopolamine on memory and attention. Neuropsychology 5, 685–700.

    Google Scholar 

  • Casamenti F., DePatre P. L., Bartolini L., and Pepeu G. (1988) Unilateral and bilateral nucleus basalis lesions: Differences in neurochemical and behavioral recovery. Neuroscience 2, 209–215.

    Article  Google Scholar 

  • Chrobak J. J., Hanin L, Schmechel D. E., and Walsh T. J. (1988) AF64A-induced working memory impairment: behavioral, neurochemical and histological correlates. Brain Res. 463, 107–117.

    Article  PubMed  CAS  Google Scholar 

  • Chrobak J. J., Hanin I., and Walsh T. J. (1987) AF64A (ethylcholine aziridinium ion), a cholinergic neurotoxin, selectively impairs working memory in a multiple component T-maze task. Brain Res. 414, 15–21.

    Article  PubMed  CAS  Google Scholar 

  • Chui H. C., Bondareff W., Zarow C., and Slager U. (1984) Stability of neuronal number in the human nucleus basalis of Meynert with age. Neurobiol. Aging 5, 83–88.

    Article  PubMed  CAS  Google Scholar 

  • Coffey P. J., Perry V. H., Allen Y., Sinden J., and Rawlins J. N. P. (1988) Ibotenic acid induced demyelination in the central nervous system: a consequence of a local inflammatory response. Neurosci. Lett. 84, 178–184.

    Article  PubMed  CAS  Google Scholar 

  • Collerton D. (1986) Cholinergic function and intellectual decline in Alzheimer’s disease. Neuroscience 19, 1–28.

    Article  PubMed  CAS  Google Scholar 

  • Cotman C. W. and Iversen L. L. (1987) Excitatory amino acids in the brain—focus on NMDA receptors. Trends Neurosci. 10, 263–280.

    Article  CAS  Google Scholar 

  • Coyle J. T. (1983) Neurotoxic action of kainic acid. J. Neurochem. 41, 1–11.

    Article  PubMed  CAS  Google Scholar 

  • Coyle J. T. and Schwartz R. (1983) The use of excitatory amino acids as selective neurotoxins, in Handbook of Chemical Neuroanatomy. Vol. 1: Methods in Chemical Neuroanatomy (Borklund A. and Hokfelt T., eds.), pp. 508–527. Elsevier, New York.

    Google Scholar 

  • Coyle J. T., Price D. L., and DeLong M. R. (1983) Alzheimer’s disease: A disorder of cortical cholinergic innervation. Science 219, 1184–1190.

    Article  PubMed  CAS  Google Scholar 

  • Craik F. I. M. (1977) Age differences in human memory, in The Handbook of the Psychology of Aging (Birren J. E. and Schaire K. W., eds.), pp. 384–420. Van Nostrand Reinhold, New York.

    Google Scholar 

  • Crapper McLachlan D. R. and De Boni U. (1980) Aluminum in human brain disease—An overview. Neurotoxicology 1, 3–16.

    Google Scholar 

  • Crapper D. R., Quittkat S., Krishnan S. S., Dalton A. J., and DeBoni U. (1980) Intranuclear aluminum content in Alzheimer’s disease, dialysis encephalopathy, and experimental aluminum encephalopathy. Acta Neuropthol. 50, 19–24.

    Article  CAS  Google Scholar 

  • Cross A. J., Crow T. J., Ferrier I. N., Johnson J. A., Bloom S. R., and Corsellis J. A. N. (1984) Serotonin receptor changes in dementia of the Alzheimer type. J. Neurochem. 43, 1574–1581.

    Article  PubMed  CAS  Google Scholar 

  • D’amato R. J., Zweig R. M., Whitehouse P. J., Wenk G. L., Singer H. S., Mayeux R., Price D. L., and Snyder S. H. (1987) Aminergic systems in Alzheimer’s disease and Parkinson’s disease. Ann. Neurol. 22, 229–236.

    Article  CAS  Google Scholar 

  • Davies P. and Maloney A. J. F. (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 2, 1403.

    Article  PubMed  CAS  Google Scholar 

  • Davis K. L. and Mohs R. C. (1982) Enhancement of memory processes in Alzheimer’s disease with multiple-dose intravenous physostigmine. Am.J Psychiat. 139, 1421–1424.

    PubMed  CAS  Google Scholar 

  • Decker M. W. (1987) The effects of aging on hippocampal and cortical projections of the forebrain cholinergic system. Brain Res. Rev. 12, 423–438.

    Article  CAS  Google Scholar 

  • Delaney J. F. (1979) Spinal fluid aluminum levels in patients with Alzheimer disease. Ann. Neurol. 5, 580–581.

    Article  PubMed  CAS  Google Scholar 

  • Dunea G., Mahurkar S. D., Mamdani B., and Smith E. C. (1978) Role of aluminum in dialysis dementia. Ann. Int. Med. 88, 502–504.

    Article  PubMed  CAS  Google Scholar 

  • Dunne M. P. and Hartley L. R. (1985) The effects of scopolamine upon verbal memory: evidence for an attentional hypothesis. Acta Psychol. 58, 205–217.

    Google Scholar 

  • Dunnett S. B., Low W. C., Iversen S. D., Stenevi U., and Bjorklund A. (1982) Septal transplants restore maze learning in rats with fonix-fimbria lesions. Brain Res. 251, 335–348.

    Article  PubMed  CAS  Google Scholar 

  • Dunnett S. B., Rogers D. C., and Jones G. H. (1989) Effects of nucleus basalis magnocellularis lesions in rats on delayed matching and non-matching to position tasks. Eur. J. Neurosci. 1, 395–406.

    Article  PubMed  Google Scholar 

  • Ebel A., Strosser M. T., and Kempf E. (1987) Genotypic differences in central neurotransmitter responses to aging mice. Neurobiol. Aging 8, 417–427.

    Article  PubMed  CAS  Google Scholar 

  • Etienne P., Robitaille Y., Wood P., Gauthier S., Nair N. P. V., and Quirion R, (1986) Nucleus basalis neuronal loss, neuritic plaques and choline acetyltransferase activity in advanced Alzheimer’s disease. Neurosci. 19, 1279–1291.

    Article  CAS  Google Scholar 

  • Fischer W., Gage F. H., and Bjorklund A. (1989) Degenerative changes in forebrain cholinergic nuclei correlate with cognitive impairments in aged rats. Eur. J. Neurosci. 1, 34–45.

    Article  PubMed  Google Scholar 

  • Folstein M. F. and Whitehouse P. J. (1983) Cognitive impairment of Alzheimer disease. Neurobehav. Toxicol. Teratol. 5, 631–634.

    PubMed  CAS  Google Scholar 

  • Francis P. T., Palmer A. M., Sims N. R., Bowen D. M., Davison A. N., Esiri M. M., Neary D., Snowden J. S., and Wilcock G. K. (1985) Neurochemial studies of early-onset Alzheimer’s disease. N. Engl. J. Med. 313, 7–11.

    Article  PubMed  CAS  Google Scholar 

  • Freedman M. and Oscar-Berman M. (1986) Selective delayed response deficits in Parkinson’s and Alzheimer’s disease. Arch. Neurol. 43, 886–890.

    Article  PubMed  CAS  Google Scholar 

  • Gaal G., Potter P. E., Hanin I., Kakucska I., and Vizi E. S. (1986) Effects of intracerebroventricular AF64A administration on cholinergic, serotonergic and catecholaminergic circuitry in rat dorsal hippocampus. Neuroscience 19, 1197–1205.

    Article  PubMed  CAS  Google Scholar 

  • Gage F. H., Dunnett S. B., and Bjorklund A. (1984a) Spatial learning and motor deficits in aged rats. Neurobiol. Aging 5, 43–48.

    Article  PubMed  CAS  Google Scholar 

  • Gage F. H., Kelly P. A. T., and Bjorklund A. (1984b) Regional changes in brain glucose metabolism reflect cognitive impairments in aged rats. J. Neurosci. 4, 2856–2865.

    PubMed  CAS  Google Scholar 

  • Gardiner I. M., de Belleroche J., Premi B. K., and Hamilton M. H. (1987) Effect of lesion of the nucleus basalis of rat on acetylcholine release in cerebral cortex: time course of compensatory events. Brain Res. 407, 263–271.

    Article  PubMed  CAS  Google Scholar 

  • Godefroy F., Bassant M. H., Weil-Fugazza J., and Lamour Y. (1989) Age-related changes in dopaminergic and serotonergic indices in the rat forebrain. Neurobiol. Aging 10, 187–190.

    Article  PubMed  CAS  Google Scholar 

  • Gonatas N. K., Anderson W., and Evangelista I. (1967) The contribution of altered synapses in the senile plaque: an electron microscopic study in Alzheimer’s dementia. J. Neuropathol. Exp. Neurol. 26, 25–39.

    Article  PubMed  CAS  Google Scholar 

  • Handelmann G. E. and Olton D. S. (1981) Recovery of function after neurotoxic damage to the hippocampal CA3 region: Importance of postoperative recovery interval and task experience. Behav. Neural Biol. 33, 453–464.

    Article  PubMed  CAS  Google Scholar 

  • Henderson Z. (1991) Sprouting of cholinergic axons does not occur in the cerebral cortex after nucleus basalis lesions. Neuroscience 1, 149–156.

    Article  Google Scholar 

  • Henke H. and Lang W. (1983) Cholinergic enzymes in neocortex, hippocampus and basal forebrain of non-neurological and senile dementia of Alzheimer-type patients. Brain Res. 267, 281–291.

    Article  PubMed  CAS  Google Scholar 

  • Hepler D. J., Olton D. S., Wenk G. L., and Coyle J. T. (1985) Lesions in nucleus basalis magnocellularis and medial septal area of rats produce qualitatively similar memory impairments. J. Neurosci. 5, 866–873.

    PubMed  CAS  Google Scholar 

  • Hohmann C. F. and Coyle J. T. (1988) Long-term effects of basal forebrain lesions on cholinergic, noradrenergic and serotonergic markers in mouse neocortex. Brain Res. Bull. 21, 13–20.

    Article  PubMed  CAS  Google Scholar 

  • Hohmann C. F., Wenk G. L., Lowenstein P., Brown M. E., and Coyle J. T. (1987) Age-related recurrence of basal forebrain lesion-induced cholinergic deficits. Neurosci. Lett. 82, 253–259.

    Article  PubMed  CAS  Google Scholar 

  • Hoyer S., Oesterreich K., and Wager O. (1988) Glucose metabolism as the site of the primary abnormality in early onset dementia of Alzheimer type? J. Neurol. 235, 143–148.

    Article  PubMed  CAS  Google Scholar 

  • Hyman B. T., VanHoesen G. W., Damasio A. R., and Barnes C. L. (1984) Alzheimer’s disease: Cell-specific pathology isolates the hippocampal formation. Science 225, 1168–1170.

    Article  PubMed  CAS  Google Scholar 

  • Irle E. and Markowitsch H. J. (1987) Basal forebrain-lesioned monkeys are severely impaired in tasks of association and recognition memory. Ann Neurol. 22, 735–743.

    Article  PubMed  CAS  Google Scholar 

  • Jarrard L. E., Kant G. J., Meyerhoff J. L., and Levy A. (1984) Behavioral and neurochemical effects of intraventricular AF64A administration in rats. Pharmacol. Biochem. Behav. 21, 273–280.

    Article  PubMed  CAS  Google Scholar 

  • Johnston M. V., McKinney M., and Coyle J. T. (1979) Evidence for a cholinergic projection to neocortex from neurons in the basal forebrain. Proc. Natl. Acad. Sci. USA 76, 5392–5396.

    Article  PubMed  CAS  Google Scholar 

  • Johnston M. V., McKinney M., and Coyle J. T. (1981) Neocortical cholinergic innervation in the rat. Exp. Brain Res. 43, 159–172.

    Article  PubMed  CAS  Google Scholar 

  • Kemper T. L. (1983) Organization of the neuropathology of the amygdala in Alzheimer’s disease, in Banbury Report. 15: Biological Aspects of Alzheimer’s Disease, pp. 31–35, Cold Spring Harbor Lab., Cold Spring Harbor, NY.

    Google Scholar 

  • Kidd M. (1963) Paired helical filaments in electron microscopy of Alzheimer’s disease. Nature 197, 192,193.

    Article  PubMed  CAS  Google Scholar 

  • Kitt C. A., Mitchell S. J., DeLong M. R., Wainer B. H., and Price D. L. (1987) Fiber pathways of basal forebrain cholinergic neurons in monkeys. Brain Res. 406, 192–206.

    Article  PubMed  CAS  Google Scholar 

  • Kitt C. A., Struble R. G., Cork L. C., Mobley W. C., Walker L. C., Joh T. H., and Price D. L. (1985) Catecholaminergic neurites in senile plaques in prefrontal cortex of aged nonhuman primates. Neuroscience 16, 691–699.

    Article  PubMed  CAS  Google Scholar 

  • Kiyosawa M., Pappata S., Duverger D., Riche D., Cambon H., Mazoyer B., Samson Y., Crouzel C., Naquet R., MacKenzie E.T., and Baron J-C. (1987) Cortical hypometabolism and its recovery following nucleus basalis lesions in baboons: A PET study. J. Cerebral Blod Flow Metabol. 7, 812–817.

    Article  CAS  Google Scholar 

  • Kohler C. and Schwartz R. (1983) Comparison of ibotenate and kainate neurotoxicity in rat brain: A histological study. Neuroscience 8, 819–835.

    Article  PubMed  CAS  Google Scholar 

  • Lamarca M. V. and Fibiger H. C. (1984) Deoxyglucose uptake and choline acetyltransferase activity in cerebral cortex following lesions of the nucleus basalis magnocellularis. Brain Res. 307, 366–369.

    Article  PubMed  CAS  Google Scholar 

  • Lenders M.-B., Peers M.-C., Tramu G., Delacourte A., Defossez A., Petit H., and Mazzuca M. (1989) Dystrophic peptidergic neurites in senile plaques of Alzheimer’s disease hippocampus precede formation of paired helical filaments. Brain Res. 481, 344–349.

    Article  PubMed  CAS  Google Scholar 

  • Leong S. F., Lai J. C. K., Lim L., and Clark J. B. (1981) Energy-metabolizing enzymes in brain regions of adult and aging rats. J. Neurochem. 37, 1548–1556.

    Article  PubMed  CAS  Google Scholar 

  • Levy A., Kant G. J., Meyerhoff J. L., and Jarrard L. E. (1984) Noncholinergic neurotoxic effects of AF64A in substantia nigra. Brain Res. 305, 169–172.

    Article  PubMed  CAS  Google Scholar 

  • Lindner M. D. and Schallert T. (1988) Aging and atropine effects on spatial navigation in the Morris water task. Behav. Neurosci. 102, 621–634.

    Article  PubMed  CAS  Google Scholar 

  • London E. D., McKinney M., Dam M., Ellis A., and Coyle J. T. (1984) Decreased cortical glucose utilization after ibotenate lesion of the rat ventromedial globus pallidus. J. Cerebr. Blood Flow Metab. 4, 381–390.

    Article  CAS  Google Scholar 

  • Mantione C. R., Fisher A., and Hanin I. (1981) The AF64A-treated mouse: possible model for central cholinergic hypofunction. Science 13, 579–580.

    Article  Google Scholar 

  • Markowska A. L., Stone W. S., Ingram D. K., Reynolds J., Gold P. E., Conti L. H., Pontecorvo M. J., Wenk G. L., and Olton D. S. (1989) Individual differences in aging: Behavioral and neurobiological correlates. Neurobiol. Aging 10, 31–43.

    Article  PubMed  CAS  Google Scholar 

  • Martinez J. L., Schulteis G., Janak P. H., and Weinberger S. B. (1988) Behavioral assessment of forgetting in aged rodents and its relationship to peripheral sympathetic function. Neurobiol. Aging 9, 697–708.

    Article  PubMed  Google Scholar 

  • Mason S. T. and Fibiger H. C. (1979) On the specificity of kainic acid. Science 20, 1339–1341.

    Article  Google Scholar 

  • McKhann G., Drachman D., Folstein M., Katzman R., Price D., and Stadlan E. M. (1984) Clinical diagnosis of Alzheimer’s disease. Neurology 34, 939–944.

    Article  PubMed  CAS  Google Scholar 

  • McGurk S. R., Hartgraves S. L., Kelly P. H., Gordon M. N., and Butcher L. L. (1987) Is ethylcholine mustard aziridinium ion a specific cholinergic neurotoxin? Neuroscience 22, 215–224.

    Article  PubMed  CAS  Google Scholar 

  • Mesulam M. M., Mufson E. J., Levey A. I., and Wainer B. H. (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nuclei basalis (substantia innominata) and hypothalamus in rhesus monkey. J. Comp. Neurol. 214, 170–197.

    Article  PubMed  CAS  Google Scholar 

  • Mesulam M. M., Mufson E. J., Levey A. I., and Wainer B. H. (1984) Atlas of cholinergic neurons in the forebrain and upper brainstem of the macaque based on monoclonal choline acetyltransferase immunohistochemistry and acetylcholinesterase histochemistry. Neuroscience 12, 669–686

    Article  PubMed  CAS  Google Scholar 

  • Meyers D., Armstrong R. A., Smith C. U. M., and Carter R. A. (1988) The spatial arrangement pattern of senile plaques in senile dementia of the Alzheimer type (SDAT). Neurosci. Res. Comm. 2, 99–106

    Google Scholar 

  • Michalek H., Fortuna S., and Pintor A. (1989) Age-related differences in brain choline acetyltransferase, cholinesterase and muscarinic receptor sites in two strains of rats. Neurobiol. Aging 10, 143–148.

    Article  PubMed  CAS  Google Scholar 

  • Mitchell S. J., Rawlins J. N. P., Steward O., and Olton D. S. (1982) Medial septal area lesions disrupt theta rhythm and cholinergic staining in medial entorhinal cortex and produce impaired radial arm maze behavior in rats. J. Neurosci. 2, 292–302.

    PubMed  CAS  Google Scholar 

  • Moretti A., Carfagna N., and Trunzo F. (1987) Effects of monoamines and their metabolites in the rat brain. Neurosci. Res. 12, 1035–1039.

    CAS  Google Scholar 

  • Mufson E. J., Kehr A. D., Wainer B. R, and Mesulam M.-M. (1987) Cortical effects of neurotoxic damage to the nucleus basalis in rats: persistent loss of extrinsic cholinergic input and lack of transsynaptic effect upon the number of somatostatin-containing, cholinesterase-positive, and cholinergic cortical neurons. Brain Res. 417, 385–388.

    Article  PubMed  CAS  Google Scholar 

  • Nemeroff C. B., Kizer J. S., Reynolds G. P., and Bissette G. (1989) Neuropeptides in Alzheimer’s disease: a postmortem study. Reg. Peptides 25, 123–130.

    Article  CAS  Google Scholar 

  • Ojima H., Sakurai T., and Yamasaki T. (1988) Changes in choline acetyltransferase immunoreactivity and the number of immunoreactive fibers remaining after lesions of the magnocellular basal nucleus of rats. Neurosci. Lett. 95, 31–36.

    Article  PubMed  CAS  Google Scholar 

  • Okaichi H. and Jarrard L. E. (1982) Scopolamine impairs performance of a place and cue task in rats. Behav. Neural Biol. 35, 1982.

    Article  Google Scholar 

  • Olney J. W., Rhee V., and Ho O. L. (1974) Kainic acid: a powerful neurotoxic analogue of glutamate. Brain Res. 77, 507–512.

    Article  PubMed  CAS  Google Scholar 

  • Olton D. S. (1986) Interventional approaches to memory: Lesions, in Learning and Memory: A Biological View (Martinez J. L. and Kesner R., eds.), pp. 379–397, Academic, New York.

    Chapter  Google Scholar 

  • Olton D. S., Walker J. A., and Wolf W. A. (1982) A disconnection analysis of hippocampal function. Brain Res. 233, 241–253.

    Article  PubMed  CAS  Google Scholar 

  • Olton D. S. and Wenk G. L. (1987) Dementia: Animal models of the cognitive impairments produced by degeneration of the basal forebrain cholinergic system, in Psychopharmacology: The Third Generation of Progress (Meltzer H.Y., ed.), pp. 941–953, Raven, New York.

    Google Scholar 

  • Olton D. S., Wenk G. L., Church R. M., and Meek W. H. (1988) Attention and the frontal cortex as examined by simultaneous temporal processing. Newpsychology 26, 307–318.

    Article  CAS  Google Scholar 

  • Owen M. J. and Butler S. R. (1981) Amnesia after transection of the fornix in monkeys: long-term memory impaired, short-term memory intact. Behav. Brain Res. 3, 115–123.

    Article  PubMed  CAS  Google Scholar 

  • Pearson R. C. A., Neal J. W., and Powell T. P. S. (1986) Hypertrophy of cholinergic neurones of the basal nucleus in the rat following damage of the contralateral nucleus. Brain Res. 382, 149–152.

    Article  PubMed  CAS  Google Scholar 

  • Pedata F., LoConte G., Sorbi S., Marconcini Pepeu I., and Pepeu G. (1982) Changes in high affinity choline uptake in rat cortex following lesions of the magnocellular forebrain nuclei. Brain Res. 233, 359–367.

    Article  PubMed  CAS  Google Scholar 

  • Pendlebury W. W., Beal M. F., Kowall N. W., and Soloman P. R. (1988) Neuropathologic, neurochemical and immunocytochemical characteristics of aluminum-induced neurofilamentous degeneration. Neurotoxicology 9, 503–510.

    PubMed  CAS  Google Scholar 

  • Perkins M. N. and Stone T. W. (1983) Quinolinic acid: regional variations in neuronal sensitivity. Brain Res. 259, 172–176.

    Article  PubMed  CAS  Google Scholar 

  • Perry E. K. and Perry R. H. (1985) New insights into the nature of senile (Alzheimer-type) plaques. Trends Neurosci. 10, 301–303.

    Article  Google Scholar 

  • Piercey M. F., Vogelsang G. D., Franklin S. R., and Tang A. H. (1987) Reversal of scopolamine-induced amnesia and alterations in energy metabolism by the nootropic piracetam: Implications regarding identification of brain structures involved in consolidation of memory traces. Brain Res. 42, 1–9.

    Article  Google Scholar 

  • Preston G. C., Brazell C., Ward C., Broks P., Traub M., and Stahl S. M. (1988) The scopolamine model of dementia: determination of central cholinomimetic effects of physostigmine on cognition and biochemical markers in man. J. Psychopharmacol. 2, 67–79.

    Article  PubMed  CAS  Google Scholar 

  • Price D. L. (1986) New perspectives on Alzheimer’s disease. Ann. Rev. Neurosci. 9, 489–512.

    Article  PubMed  CAS  Google Scholar 

  • Rapp P. R., Rosenberg R. A., and Gallagher M. (1987) An evaluation of spatial information processing in aged rats. Behav. Neurosci. 101, 3–12.

    Article  PubMed  CAS  Google Scholar 

  • Ridley R. M., Baker H. F., Drewett B., and Johnson J. A. (1985) Effects of ibotenic acid lesions of the basal forebrain serial reversal learning in marmosets. Psychopharmacology 86, 438–443.

    Article  PubMed  CAS  Google Scholar 

  • Ridley R. M., Murray T. K., Johnson J. A., and Baker H. F. (1986) Learning impairment following lesion of the basal nucleus of Meynert in the marmoset: Modification by cholinergic drugs. Brain Res. 376, 108–116.

    Article  PubMed  CAS  Google Scholar 

  • Roudier M., Marcie P., Podrabinek N., Lamour Y., and Davous P. (1988) Correlations between memory, language, agnosia, and apraxia in 80 patients with senile dementia of the Alzheimer type. Drug Develop. Res. 14, 231–234.

    Article  Google Scholar 

  • Rusted J. M. (1988) Dissociative effects of scopolamine on working memory in healthy young volunteers. Psychopharmacology 96, 487–492.

    Article  PubMed  CAS  Google Scholar 

  • Saletu B., Grunberger J., Linzmayer L., and Anderer P. (1979) Proof of CNS efficacy and pharmacodynamics of nicergoline in the elderly by acute and chronic quantitative pharmaco-EEG and psychometric studies, in Drug Treatment and Prevention in Cerebrovascular Disorders (Tognoni G. and Garattini S., eds.), pp. 245–272, Elsevier/North Holland, Amsterdam.

    Google Scholar 

  • Sandberg K., Hanin I., Fisher A., and Coyle J. T. (1984) Selective cholinergic neurotoxin: AF64A’s effects in rat striatum. Brain Res. 293, 49–55.

    Article  PubMed  CAS  Google Scholar 

  • Sandberg K., Schnaar R. L., McKinney M., Hanin I., Fisher A., and Coyle J. T. (1985) AF64A: An active site directed irreversible inhibitor of choline acetyltransferase. J. Neurochem. 44, 439–445.

    Article  PubMed  CAS  Google Scholar 

  • Satoh K. and Fibiger H. C. (1985) Distribution of central cholinergic neurons in the baboon (Papio): I. General morphology. J. Comp. Neurol. 236, 197–214.

    Article  PubMed  CAS  Google Scholar 

  • Schwartz R. and Kohler C. (1983) Differential vulnerability of central neurons of the rat to quinolinic acid. Neurosci. Lett. 38, 85–90.

    Article  Google Scholar 

  • Schwartz R., Scholz D., and Coyle J. T. (1978) Structure-activity relations for the neurotoxicity of kainic acid derivatives and glutamate analogues. Neuropharmacology 17, 145–151.

    Article  Google Scholar 

  • Simon J. R. and Kuhar M. J. (1975) Impulse-flow regulation of high affinity choline uptake in brain cholinergic nerve terminal. Nature 255, 162–163.

    Article  PubMed  CAS  Google Scholar 

  • Sirvio J., Valjakka A., Jolkkonen J., Jervonen A., and Riekkinen P. J. (1988) Cholinergic enzyme activities and muscarinic binding in the cerebral cortex of rats of different age and sex. Comp. Biochem. Physiol. 90C, 245–248.

    CAS  Google Scholar 

  • Smith C. M. and Swash M. (1978) Possible biochemical basis of memory disorder in Alzheimer Disease. Ann. Neurol. 3, 471–473.

    Article  PubMed  CAS  Google Scholar 

  • Smith G. (1988) Animal models of Alzheimer’s disease: experimental cholinergic denervation. Brain Res. Rev. 13, 103–118.

    Article  Google Scholar 

  • Spangler E. L., Rigby P., and Ingram D. K. (1986) Scopolamine impairs learning performance of rats in a 14-unit T-maze. Pharmcol. Biochem. Behav. 25, 673–679.

    Article  CAS  Google Scholar 

  • Spignoli G. and Pepeu G. (1987) Interactions between oxiracetam, aniracetam and scopolamine on behavior and brain acetylcholine. Pharmacol. Biochem. Behav. 27, 491–495.

    Article  PubMed  CAS  Google Scholar 

  • Struble R. G., Cork L. C., Whitehouse P. J., and Price D. L. (1982) Cholinergic innervation of neuritic plaques. Science 216, 413–415.

    Article  PubMed  CAS  Google Scholar 

  • Struble R. G., Powers R. E., Casanova M. F., Kitt C. A., Brown E. C., and Price D. L. (1987) Neuropeptidergic systems in plaques of Alzheimer’s disease. J. Neuropathol. Exp. Neurol. 46, 567–584.

    Article  PubMed  CAS  Google Scholar 

  • Struble R. G., Price Jr., D. L., Cork L. C., and Price D. L. (1985) Senile plaques in cortex of aged normal monkeys. Brain Res. 361, 267–275.

    Article  PubMed  CAS  Google Scholar 

  • Summers W. K., Majovski L. V., Marsh G. M., Tachiki K., and Kling A. (1987) Oral tetrahydroaminoacridine in long-term treatment of Alzheimer’s disease. New Engl. J. Med. 315, 1241–1245.

    Article  Google Scholar 

  • Tay S. S. W., Williams T. H., and Jew J.Y. (1989) Neurotensin immunoreactivity in the central nucleus of the rat amygdala: An ultrastructural approach. Peptides 10, 113–120.

    Article  PubMed  CAS  Google Scholar 

  • Terry R. D. and Davies P. (1980) Dementia of the Alzheimer type. Ann. Rev. Neurosci. 3, 77–95.

    Article  PubMed  CAS  Google Scholar 

  • Terry R. D. and Pena C. (1965) Experimental production of neurofibrillary degeneration. Neuropathol. Exp. Neural. 24, 200–210.

    Article  CAS  Google Scholar 

  • Terry R. D., Mandel R. J., Buzsaki G., Gage F. H., and Thal L. J. (1988) Characterization of the effects of nucleus basalis lesions in rats 14 months post-lesion. Soc. Neurosci. Abstr. 1, 1007.

    Google Scholar 

  • Thal L. J., Rosen W, and Sharpless N. S. (1981) Choline chloride fails to improve cognition in Alzheimer’s disease. Neurobiol. Aging 2, 205–208.

    Article  PubMed  CAS  Google Scholar 

  • Trapp G. A., Miner G. D., Zimmerman R. L., Mastri A. R., and Heston L. L. (1978) Aluminum levels in brain in Alzheimer’s disease. Biol. Psychiat. 13, 709–718.

    PubMed  CAS  Google Scholar 

  • Troncoso J. G, Price D. L., Griffin J. W., and Parhad I. M. (1982) Neurofibrillary axonal pathology in aluminum intoxication. Ann. Neurol. 12, 278–283.

    Article  PubMed  CAS  Google Scholar 

  • Tucek S. (1978) Acetylcholine Synthesis in Neurons. Chapman and Hall, London.

    Google Scholar 

  • Ulrich J. and Stahelin H. B. (1984) The variable topography of Alzheimer type changes in senile dementia and normal old age. Gerontology 30, 210–214.

    Article  PubMed  CAS  Google Scholar 

  • Vanella A., Villa R. F., Gorini A., Campisi A., and Giuffrida-Stella A. M. (1989) Superoxide dismutase and cytochrome oxidase activities in light and heavy synaptic mitochondria from rat cerebral cortex during aging. J. Neurosci. Res. 22, 351–355.

    Article  PubMed  CAS  Google Scholar 

  • Villani L., Contestabile A., Migani P., Poli A., and Fonnum F. (1986) Ultra-structural and neurochemical effects of the presumed cholinergic toxin AF64A in the rat interpeduncular nucleus. Brain Res. 379, 223–231.

    Article  PubMed  CAS  Google Scholar 

  • Walker L. C., Kitt C. A., Cork L. C., Struble R. G., Dellovade T. L., and Price D. L. (1988a) Multiple transmitter systems contribute neurites to individual senile plaques. J. Neuropathol. Exe. Neurol. 47, 138–144.

    Article  CAS  Google Scholar 

  • Walker L. C., Kitt C. A., Struble R. G., Wagster M. V., Price D. L., and Cork, L. C. (1988b) The neural basis of memory decline in aged monkeys. Neurobiol. Aging 9, 657–666.

    Article  PubMed  CAS  Google Scholar 

  • Walker L. C., Koliatsos V. E., Kitt G A., Richardson R. T., Rokaeus A., and Price D. L. (1989) Peptidergic neurons in the basal forebrain magnocellular complex of the rhesus monkey. J. Comp. Neurol. 280, 272–282.

    Article  PubMed  CAS  Google Scholar 

  • Wenk G. L. (1989) An hypothesis on the role of glucose in the mechanism of action of cognitive enhancers. Psychopharmcology 99, 431–438.

    Article  CAS  Google Scholar 

  • Wenk G. L., Cribbs B., and McCall L. (1984) Nucleus basalis magnocellularis: Optimal coordinates for selective reduction of choline acetyltransferase in frontal neocortex by ibotenic acid injections. Ex. Brain Res. 56, 335–340.

    CAS  Google Scholar 

  • Wenk G. L. and Engisch K. L. (1986) [3H] Ketanserin (serotonin type 2) binding increases in rat cortex following basal forebrain lesions with ibotenic acid. J. Neurochem. 47, 845–850.

    Article  PubMed  CAS  Google Scholar 

  • Wenk G. L., Engisch K. L., McCall L. D., Mitchell S. J., Aigner T. G., Struble R. L., Price D. L., and Olton D. S. (1986) [3H] Ketanserin binding increases in monkey cortex following basal forebrain lesions with ibotenic acid. Neurochem. Int. 9, 557–562.

    Article  PubMed  CAS  Google Scholar 

  • Wenk G. L., Hughey D., Boundy V., Kim A., Walker L., and Olton D. (1987) Neurotransmitters and memory: Role of cholinergic, serotonergic, and noradrenergic systems. Behav. Neurosci. 101, 325–332.

    Article  PubMed  CAS  Google Scholar 

  • Wenk G. L., Markowska A. L., and Olton D. S. (1989a) Basal forebrain lesions and memory: Alterations in neurotensin, not acetylcholine, may cause amnesia. Behav. Neurosci. 103, 765–769.

    Article  PubMed  CAS  Google Scholar 

  • Wenk G. L. and Olton D. S. (1984) Recover of neocortical choline acetyltransferase activity following ibotenic acid injection in the nucleus basalis of Meynert in rats. Brain Res. 293, 184–186.

    Article  PubMed  CAS  Google Scholar 

  • Wenk G. L. and Olton D. S. (1987) Basal forebrain cholinergic neurons and Alzheimer’s disease, in Animal Models of Dementia (Coyle J.T., ed.), pp. 81–101, Liss, New York.

    Google Scholar 

  • Wenk G. L., Pierce D. J., Struble R. G., Price D. L., and Cork L. C. (1989b) Age-related changes in multiple neurotransmitter systems in the monkey brain. Neurobiol. Aging 10, 11–19.

    Article  PubMed  CAS  Google Scholar 

  • Wenk G. L. and Rokaeus A. (1988) Basal forebrain lesions differentially alter galanin levels and acetylcholinergic receptors in the hippocampus and neocortex. Brain Res. 460, 17–21.

    Article  PubMed  CAS  Google Scholar 

  • Wesnes K. and Warburton D. M. (1983) Effects of scopolamine on stimulus sensitivity and response in a visual vigilance task. Neuropsychobiology 9, 154–157.

    Article  PubMed  CAS  Google Scholar 

  • Wesnes K. and Warburton D. M. (1984) Effects of scopolamine and nicotine on human rapid information processing performance. Psychopharmacology 82, 147–150.

    Article  PubMed  CAS  Google Scholar 

  • Whitehouse P. J., Price D. L., Clark A. W., Coyle J. T., and DeLong M. R. (1981) Alzheimer Disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann. Neurol. 10, 122–126.

    Article  PubMed  CAS  Google Scholar 

  • Whitehouse P. J,, Struble R. G., Hedreen J. C., Clark A. W., and Price D. L. (1985) Alzheimer’s disease and related dementias: selective involvement of specific neuronal systems. CRC Critical Rev. Clin. Neurobiol. 1, 319–339.

    CAS  Google Scholar 

  • Yates C. M., Simpson J., Gordon A., Maloney A. F. J., Allison Y., Ritchie I. M., and Urquhart A. (1983) Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down’s syndrome. Brain Res 280, 119–126.

    Article  PubMed  CAS  Google Scholar 

  • Yokel R. A. (1983) Repeated systemic aluminum exposure effects on classical conditioning of the rabbit. Neurobehav. Toxicol. Teratol. 5, 41–46.

    PubMed  CAS  Google Scholar 

  • Yokel R. A., Provan S. D., Meyer J. J., and Campbell S. R. (1988) Aluminum intoxication and the victim of Alzheimer’s disease: similarities and differences. Neurotoxicology 9, 429–442.

    PubMed  CAS  Google Scholar 

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Wenk, G.L. (1992). Animal Models of Alzheimer’s Disease. In: Boulton, A.A., Baker, G.B., Butterworth, R.F. (eds) Animal Models of Neurological Disease, I. Neuromethods, vol 21. Humana Press, Totowa, NJ. https://doi.org/10.1385/0-89603-208-6:29

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