title: Quantitative synaptic alterations in the human neocortex during normal aging.
abstract: We quantified the synaptic population density in the frontal cortex of 25 individuals without dementia 16 to 98 years old, using sections double-immunolabeled for beta/A4 amyloid and for synaptophysin, and found a significant inverse correlation between the presynaptic terminal (PT) counts and age (r = -0.7, p < 0.001). Individuals older than 60 years had an average 20% decrease in PT density compared with individuals younger than 60 years. There were no significant correlations between the age and the number of beta/A4 amyloid-positive plaques or between synaptic density and the number of amyloid plaques. Further analysis of the digitized serial optical images showed focal areas of synapse loss and distended synaptophysin-containing boutons in the mature plaques of the normal aged cases. However, we found no microscopic changes in the synaptic content inside and outside the diffuse plaques. We suggest that a loss of synaptic input in the neocortex is an age-dependent factor that contributes to the overall synaptic loss in Alzheimer's disease, but that this might be largely independent of the beta/A4-amyloid deposition.
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla 92093-0624.
authors.forename: E
authors.initials: E
authors.lastname: Masliah
authors.forename: M
authors.initials: M
authors.lastname: Mallory
authors.forename: L
authors.initials: L
authors.lastname: Hansen
authors.forename: R
authors.initials: R
authors.lastname: DeTeresa
authors.forename: R D
authors.initials: RD
authors.lastname: Terry
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000682:Amyloid / Q000032:analysis; D002540:Cerebral Cortex / Q000166:cytology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008875:Middle Aged; D012016:Reference Values; D013569:Synapses
chemical_list: D000682:Amyloid