Regionally specific loss of neurons in the aging human hippocampus

New highly-accurate stereological methods for estimating the total numbers of neurons in brain structures have been used to test for age-related neuron loss in the human hippocampal formation. Across the age range of 13 to 85 years, there was a substantial loss of neurons in the subiculum (52%) and in the hilus of the dentate gyrus (31%); the three remaining hippocampal subdivisions showed no significant change. These losses qualify as potential morphological correlates of senescent decline in relational memory in that they can be expected to compromise the functional integrity of a region of the brain known to be intimately involved in this type of memory. The regional pattern of neuron loss is similar in certain respects to the patterns of cell loss seen during the initial phases of ischemia and epilepsy and is fundamentally different from the pattern associated with Alzheimer's disease.

[1]  R. S. Sloviter,et al.  Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: The “dormant basket cell” hypothesis and its possible relevance to temporal lobe epilepsy , 1991, Hippocampus.

[2]  V. Chan‐Palay.  Somatostatin immunoreactive neurons in the human hippocampus and cortex shown by immunogold/silver intensification on vibratome sections: Coexistence with neuropeptide Y neurons, and effects alzheimer‐type dementia , 1987, The Journal of comparative neurology.

[3]  Bradley T. Hyman,et al.  Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease , 1992, Neurology.

[4]  R. Morris,et al.  Place navigation impaired in rats with hippocampal lesions , 1982, Nature.

[5]  S. Gould,et al.  Allometry in primates, with emphasis on scaling and the evolution of the brain. , 1975, Contributions to primatology.

[6]  B. McNaughton,et al.  Comparison of spatial and temporal characteristics of neuronal activity in sequential stages of hippocampal processing. , 1990, Progress in brain research.

[7]  Marion Perlmutter,et al.  Spatial and Temporal Memory in 20 and 60 Year Olds , 1981 .

[8]  D. Park,et al.  Memory for pictures, words, and spatial location in older adults: evidence for pictorial superiority. , 1983, Journal of gerontology.

[9]  David M. A. Mann,et al.  The neuropathology of Alzheimer's disease: A review with pathogenetic, aetiological and therapeutic considerations , 1985, Mechanisms of Ageing and Development.

[10]  H. J. G. Gundersen,et al.  The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis , 1988, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[11]  E. Mufson,et al.  Alz‐50 immunoreactive neuropil differentiates hippocampal complex subfields in Alzheimer's disease , 1991, The Journal of comparative neurology.

[12]  G. V. Van Hoesen,et al.  Hippocampal formation: anatomy and the patterns of pathology in Alzheimer's disease. , 1990, Progress in brain research.

[13]  H. J. G. GUNDERSEN,et al.  Some new, simple and efficient stereological methods and their use in pathological research and diagnosis , 1988, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[14]  B. McNaughton,et al.  Hippocampal synaptic enhancement and information storage within a distributed memory system , 1987, Trends in Neurosciences.

[15]  H. Gundersen,et al.  Unbiased stereological estimation of the number of neurons in the human hippocampus , 1990, The Journal of comparative neurology.

[16]  R. Sapolsky.  Chapter 2 Glucocorticoids, hippocampal damage and the glutamatergic synapse , 1990 .

[17]  B. Milner,et al.  Disorders of learning and memory after temporal lobe lesions in man. , 1972, Clinical neurosurgery.

[18]  A. R. Damasio,et al.  Pathological alterations in the amygdala in Alzheimer's disease , 1990, Neuroscience.

[19]  R. Mohs,et al.  Consortium to establish a registry for Alzheimer's disease (CERAD) clinical and neuropsychological assessment of Alzheimer's disease. , 2002, Psychopharmacology bulletin.

[20]  Mark J. West,et al.  New stereological methods for counting neurons , 1993, Neurobiology of Aging.

[21]  Hippocampal Histopathology — A Critical Substrate for Dementia of the Alzheimer Type , 1988 .

[22]  L M Cruz-Orive,et al.  Application of the Cavalieri principle and vertical sections method to lung: estimation of volume and pleural surface area , 1988, Journal of microscopy.

[23]  M. Witter,et al.  Heterogeneity in the Dorsal Subiculum of the Rat. Distinct Neuronal Zones Project to Different Cortical and Subcortical Targets , 1990, The European journal of neuroscience.

[24]  F. Geneser.  Distribution of acetylcholinesterase in the hippocampal region of the rabbit: III. The dentate area , 1987, The Journal of comparative neurology.

[25]  H. Scharfman,et al.  Similarities in circuitry between Ammon's horn and dentate gyrus: local interactions and parallel processing. , 1990, Progress in brain research.

[26]  Paul D. Coleman,et al.  Neuron numbers and dendritic extent in normal aging and Alzheimer's disease , 1987, Neurobiology of Aging.

[27]  C. B. Cave,et al.  Equivalent impairment of spatial and nonspatial memory following damage to the human hippocampus , 1991, Hippocampus.

[28]  Involutional and developmental implications of age-related neuronal changes: in search of an engram for wisdom , 1987, Neurobiology of Aging.

[29]  L. Swanson,et al.  Anatomical evidence for direct projections from the entorhinal area to the entire cortical mantle in the rat , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  L. Squire,et al.  Memory impairment in monkeys following lesions limited to the hippocampus. , 1986, Behavioral neuroscience.

[31]  L. Squire,et al.  Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  Bradley T. Hyman,et al.  Distribution of Alzheimer‐type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease , 1992, Neurology.

[33]  B. Tomlinson.  SECOND DOROTHY S. RUSSELL MEMORIAL LECTURE THE NEUROPATHOLOGY OF ALZHEIMER'S DISEASE–ISSUES IN NEED OF RESOLUTION * , 1989, Neuropathology and applied neurobiology.

[34]  Z. Khachaturian.  Diagnosis of Alzheimer's disease. , 1985, Archives of neurology.

[35]  Carl W. Cotman,et al.  Anatomical organization of excitatory amino acid receptors and their pathways , 1987, Trends in Neurosciences.

[36]  S. M. Sumi,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1991, Neurology.

[37]  H. Gundersen.  Stereology of arbitrary particles * , 1986, Journal of microscopy.

[38]  Douglas L. Rosene,et al.  The Hippocampal Formation of the Primate Brain , 1987 .

[39]  J. H. Kim,et al.  Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy , 1989, Brain Research.

[40]  L. Nadel.  The hippocampus and space revisited , 1991, Hippocampus.

[41]  W. Schlote,et al.  Rating of the lesions in senile dementia of the Alzheimer type: concordance between laboratories A European multicenter study under the auspices of EURAGE , 1990, Journal of the Neurological Sciences.

[42]  D. Amaral,et al.  The three-dimensional organization of the hippocampal formation: A review of anatomical data , 1989, Neuroscience.

[43]  C. Geula,et al.  Acetylcholinesterase‐rich pyramidal neurons in the human neocortex and hippocampus: Absence at birth, development during the life span, and dissolution in Alzheimer's disease , 1988, Annals of neurology.

[44]  J. O’Keefe,et al.  A computational theory of the hippocampal cognitive map. , 1990, Progress in brain research.