Life and Death of Neurons in the Aging Brain

Author:

Morrison John H.1,Hof Patrick R.1

Affiliation:

1. J. H. Morrison is with the Neurobiology of Aging Laboratories, the Fishberg Research Center for Neurobiology, and the Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, NY 10029, USA. P. R. Hof is with the Neurobiology of Aging Laboratories, the Fishberg Research Center for Neurobiology, the Department of Geriatrics and Adult Development, and the Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029, USA.

Abstract

Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference184 articles.

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2. Mirra S. S., Hart M. N., Terry R. D., Arch. Pathol. Lab. Med. 117, 132 (1993).

3. A panel of neuropathologists convened by the National Institute on Aging and the Ronald and Nancy Reagan Institute of the Alzheimer's Association recently developed a set of recommendations for postmortem diagnosis of AD [ Neurobiol. Aging in press]. There are several key points made in this important document among them that neurofibrillary pathology occurs in a limited fashion in many aged individuals that do not have dementia. Also the degree to which these pathologic changes are diagnostic of AD is dependent on their regional location and density. Thus given that NFT and neuropil threads can be present in neurologically normal individuals and that their distribution and density constitute a more reliable correlate of AD than their absolute presence or absence we prefer to consider such profiles as reflecting neurofibrillary pathology rather than referring to them as AD-related changes or AD lesions.

4. P. R. Hof and J. H. Morrison in Alzheimer Disease R. D. Terry R. Katzman K. L. Bick Eds. (Raven New York 1994) pp. 197-229

5. J. Am. Geriatr. Soc. 44 857 (1996);

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