Selective vulnerability of corticocortical and hippocampal circuits in aging and Alzheimer's disease

John Morrison, Patrick R. Hof

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

Alzheimer's disease (AD), a classic neurodegenerative disorder, is characterized by extensive yet selective neuron death in the neocortex and hippocampus that leads to dramatic decline in cognitive abilities and memory. Crucial subsets of pyramidal cells and their projections are particularly vulnerable. A more modest disruption of memory occurs often in normal aging, yet such functional decline does not appear to be accompanied by significant neuron death. However, the same circuits that are devastated through degeneration in AD are vulnerable to sublethal age-related biochemical and morphologic shifts that alter synaptic transmission, and thereby impair function. For example, in the monkey neocortex, pyramidal cells that are homologous to those that degenerate in AD do not degenerate with aging, yet they lose spines, suggesting that an age-related synaptic disruption has occurred. Such age-related synaptic alterations have also been reported in hippocampus. For example, NMDA receptors are decreased in certain hippocampal circuits with aging. NMDA receptors are also responsive to circulating estrogen levels, thus interactions between reproductive senescence and brain aging may also affect excitatory synaptic transmission in the hippocampus. Thus, the aging synapse may be the key to age-related memory decline, whereas neuron death is the more prominent and problematic culprit in AD.

Original languageEnglish (US)
Pages (from-to)467-486
Number of pages20
JournalProgress in Brain Research
Volume136
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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Alzheimer Disease
Hippocampus
Pyramidal Cells
Neocortex
N-Methyl-D-Aspartate Receptors
Neurons
Synaptic Transmission
Aptitude
Neurodegenerative Diseases
Synapses
Haplorhini
Estrogens
Spine
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Selective vulnerability of corticocortical and hippocampal circuits in aging and Alzheimer's disease. / Morrison, John; Hof, Patrick R.

In: Progress in Brain Research, Vol. 136, 01.01.2002, p. 467-486.

Research output: Contribution to journalArticle

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