Plasticity of hippocampal circuitry in Alzheimer's disease.

Two markers of neuronal plasticity were used to compare the response of the human central nervous system to neuronal loss resulting from Alzheimer's disease with the response of rats to a similar neuronal loss induced by lesions. In rats that had received lesions of the entorhinal cortex, axon sprouting of commissural and associational fibers into the denervated molecular layer of the dentate gyrus was paralleled by a spread in the distribution of tritiated kainic acid-binding sites. A similar expansion of kainic acid receptor distribution was observed in hippocampal samples obtained postmortem from patients with Alzheimer's disease. An enhancement of acetylcholinesterase activity in the dentate gyrus molecular layer, indicative of septal afferent sprouting, was also observed in those patients with a minimal loss of cholinergic neurons. These results are evidence that the central nervous system is capable of a plastic response in Alzheimer's disease. Adaptive growth responses occur along with the degenerative events.

[1]  C. Cotman,et al.  Recovery of spontaneous alternation following lesions of the entorhinal cortex in adult rats: possible correlation to axon sprouting. , 1977, Behavioral biology.

[2]  O. Steward,et al.  Histochemical evidence for a post‐lesion reorganization of cholinergic afferents in the hippocampal formation of the mature cat , 1978, The Journal of comparative neurology.

[3]  J. Coyle,et al.  Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. , 1982, Science.

[4]  O. Steward,et al.  The time course of changes in open field activity following bilateral entorhinal lesions in rats and cats. , 1981, Behavioral and neural biology.

[5]  D L Price,et al.  Alzheimer's disease: a disorder of cortical cholinergic innervation. , 1983, Science.

[6]  C. Cotman,et al.  Distribution of [3H]AMPA binding sites in rat brain as determined by quantitative autoradiography , 1984, Brain Research.

[7]  J. Storm-Mathisen Choline acetyltransferase and acetylcholinesterase in fascia dentata following lesion of the entorhinal afferents. , 1974, Brain research.

[8]  E. Perry,et al.  Histochemical observations on cholinesterase activities in the brains of elderly normal and demented (Alzheimer-type) patients. , 1980, Age and ageing.

[9]  C. Cotman,et al.  Replacement of damaged cortical projections by homotypic transplants of entorhinal cortex , 1985, The Journal of comparative neurology.

[10]  P. Davies,et al.  SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE , 1976, The Lancet.

[11]  G. Lynch,et al.  Time-dependent changes in commissural field potentials in the dentate gyrus following lesions of the entorhinal cortex in adult rats , 1975, Brain Research.

[12]  J. Zimmer,et al.  Extended commissural and ipsilateral projections in postnatally deentorhinated hippocampus and fascia dentata demonstrated in rats by silver impregnation. , 1973, Brain research.

[13]  D. Bowen,et al.  Dementia in the Elderly: Biochemical Aspects , 1984, Journal of the Royal College of Physicians of London.

[14]  G. Lynch,et al.  Induced acetylcholinesterase-rich layer in rat dentate gyrus following entorhinal lesions. , 1972, Brain research.

[15]  G. Lynch,et al.  Synaptic rearrangement in the dentate gyrus: histochemical evidence of adjustments after lesions in immature and adult rats. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[16]  C. Cotman,et al.  l-[3H]Glutamate binds to kainate-, NMDA- and AMPA-sensitive binding sites: an autoradiographic analysis , 1985, Brain Research.

[17]  V. Hachinski,et al.  A NEW DEFINITION OF ALZHEIMER'S DISEASE: A HIPPOCAMPAL DEMENTIA , 1985, The Lancet.

[18]  E. Perry,et al.  A cholinergic connection between normal aging and senile dementia in the human hippocampus , 1977, Neuroscience Letters.

[19]  C. Cotman,et al.  Anatomical distributions of four pharmacologically distinct 3H-L-glutamate binding sites , 1983, Nature.

[20]  R. DeTeresa,et al.  Some morphometric aspects of the brain in senile dementia of the alzheimer type , 1981, Annals of neurology.

[21]  L. Iversen,et al.  Neurochemical characteristics of early and late onset types of Alzheimer's disease. , 1984, British medical journal.

[22]  R. Terry,et al.  Senile dementia of the Alzheimer type , 1983, Annals of neurology.

[23]  C. Cotman,et al.  The distribution of [3H]kainic acid binding sites in rat CNS as determined by autoradiography , 1982, Brain Research.

[24]  E. Spokes,et al.  Post‐mortem stability of dopamine. glutamate decarboxylase and choline acetyltransferase in the mouse brain under conditions simulating the handling of human autopsy material , 1978, Journal of neurochemistry.

[25]  J. Penney,et al.  Alterations in L-glutamate binding in Alzheimer's and Huntington's diseases. , 1985, Science.

[26]  O. Steward,et al.  Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: Recovery of alternation performance following unilateral entorhinal cortex lesions , 1977, Brain Research Bulletin.

[27]  R. Marchbanks Biochemistry of Alzheimer's Dementia , 1982, Journal of neurochemistry.

[28]  B. Winblad,et al.  Changes in the Brain Catecholamines in Patients with Dementia of Alzheimer Type , 1979, British Journal of Psychiatry.

[29]  F. Bloom,et al.  Somatostatin immunoreactivity in neuritic plaques of Alzheimer's patients , 1985, Nature.

[30]  C. Cotman,et al.  Brain function, synapse renewal, and plasticity. , 1982, Annual review of psychology.

[31]  W. Bondareff,et al.  Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia , 1982, Neurology.

[32]  O. Steward,et al.  Assessing the functional significance of lesion-induced neuronal plasticity. , 1982, International review of neurobiology.

[33]  D. Mann,et al.  Changes in nerve cells of the nucleus basalis of Meynert in Alzheimer's disease and their relationship to ageing and to the accumulation of lipofuscin pigment , 1984, Mechanisms of Ageing and Development.

[34]  N Butters,et al.  Cortical Afferents to the Entorhinal Cortex of the Rhesus Monkey , 1972, Science.

[35]  G. V. Hoesen,et al.  The parahippocampal gyrus: New observations regarding its cortical connections in the monkey , 1982, Trends in Neurosciences.

[36]  W. Freed,et al.  Promoting functional plasticity in the damaged nervous system. , 1985, Science.

[37]  J. Coyle,et al.  Neurotransmitter specific alterations in dementing disorders: insights from animal models. , 1984, Journal of psychiatric research.

[38]  B. Meldrum Possible therapeutic applications of antagonists of excitatory amino acid neurotransmitters. , 1985, Clinical science.

[39]  H. Henke,et al.  Cholinergic enzymes in neocortex, hippocampus and basal forebrain of non-neurological and senile dementia of alzheimer-type patients , 1983, Brain Research.

[40]  O. Steward,et al.  Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat , 1976, The Journal of comparative neurology.

[41]  G. Lynch,et al.  Changes in the distribution of the dentate gyrus associational system following unilateral or bilateral entorhinal lesions in the adult rat , 1976, Brain Research.

[42]  C. Cotman,et al.  Synaptic localization of kainic acid binding sites , 1981, Nature.

[43]  Y. Ben-Ari,et al.  Autoradiographic visualization of [3H]kainic acid receptor subtypes in the rat hippocampus , 1983, Neuroscience Letters.

[44]  G. V. Van Hoesen,et al.  Alzheimer's disease: cell-specific pathology isolates the hippocampal formation. , 1984, Science.

[45]  P J Whitehouse,et al.  Effects of Postmortem Delay and Temperature on Neurotransmitter Receptor Binding in a Rat Model of the Human Autopsy Process , 1984, Journal of neurochemistry.

[46]  M. Mesulam,et al.  Tracing neural connections of human brain with selective silver impregnation. Observations on geniculocalcarine, spinothalamic, and entorhinal pathways. , 1979, Archives of neurology.

[47]  C. Cotman,et al.  Cell biology of synaptic plasticity. , 1984, Science.