Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment
Document Type
Article
Abstract
One of the major neuropathological findings in the brains of individuals with Alzheimer's disease (AD) is a loss of synaptic contacts in both the neocortex and hippocampus. Here we report, for the first time, an estimate of the total number of synapses in the outer molecular layer (OML) of the human dentate gyrus, in individuals with early Alzheimer's disease (eAD), mild cognitive impairment (MCI), or no cognitive impairment (NCI). An unbiased stereologic sampling scheme coupled with transmission electron microscopy to directly visualize synaptic contacts, was used to estimate the total number of synapses in short postmortem autopsy tissue. Individuals with eAD had significantly fewer synapses than the other two diagnostic groups. Seventy-five percent of the individuals with MCI had synaptic values that were lower than the NCI group mean. The number of synapses showed a significant correlation with the subject's Mini-Mental State score and with cognitive tests involving delayed recall. Synaptic loss showed no relationship to Braak stage or to apoE genotype. The volume of the OML was significantly reduced in eAD compared to the other two diagnositic groups that were not different from each other. These data suggest that a loss of afferents from the entorhinal cortex underlie the synapse loss seen in eAD. This study supports the concept that synapse loss is an early event in the disease process and suggests that MCI may be a transition stage between eAD and NCI with synaptic loss a structural correlate involved in cognitive decline. © 2005 Elsevier Inc. All rights reserved.
Keywords
Aging, Cognition, Hippocampus, Limbic system, Memory, Synapse
Publication Date
10-1-2006
Publication Title
Neurobiology of Aging
ISSN
01974580
Volume
27
Issue
10
First Page
1372
Last Page
1384
PubMed ID
16289476
Digital Object Identifier (DOI)
10.1016/j.neurobiolaging.2005.09.012
Recommended Citation
Scheff, Stephen W.; Price, Douglas A.; Schmitt, Frederick A.; and Mufson, Elliott J., "Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment" (2006). Translational Neuroscience. 1835.
https://scholar.barrowneuro.org/neurobiology/1835