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26 - Neuropathology of normal aging in cerebral cortex

from Normal aging

Published online by Cambridge University Press:  04 August 2010

M. Flint Beal
Cornell University, New York
Anthony E. Lang
University of Toronto
Albert C. Ludolph
Universität Ulm, Germany
John H. Morrison
Department of Neuroscience, Mount Sinai School of Medicine, NY, USA
Patrick R. Hof
Department of Neuroscience, Mount Sinai School of Medicine, NY, USA
Peter R. Rapp
Department of Neuroscience, Mount Sinai School of Medicine, NY, USA
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In order to understand the neuropathology of normal aging, it is instructive to review the major elements of circuit degeneration associated with Alzheimer's disease. AD is characterized by senile plaque (SP) and neurofibrillary tangle (NFT) formation and extensive, yet selective, neuron death in the hippocampus and neocortex that leads to dramatic decline in cognitive abilities and memory. A more modest disruption of memory, referred to as mild cognitive impairment (MCI) or age-associated memory impairment (AAMI), occurs often in the context of normal aging, in humans, monkeys and rodents. However, unlike AD, significant neuron death does not appear to be the cause of AAMI. In AD, the neurons providing the connection between the entorhinal cortex and the dentate gyrus (e.g. the perforant path) are devastated, as are the neurons providing corticocortical circuits that interconnect association regions. Whereas the death of these same neurons appears to be minimal in normal aging, these same circuits and the corresponding circuits in animal models are vulnerable to sublethal age-related alterations in morphology, neurochemical phenotype and synaptic integrity that might impair function. Biochemical alterations of the synapse, such as shifts in distribution or abundance of NMDA receptors, may also contribute to memory impairment. The same brain regions are also responsive to circulating estrogen levels, and thus, critical interactions between reproductive senescence and brain aging may affect excitatory synaptic transmission in the hippocampus. Importantly, some of the effects of estrogen on these neurons imply that certain synaptic alterations that accompany aging may be reversible.

Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 396 - 406
Publisher: Cambridge University Press
Print publication year: 2005

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