Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment

S. W. Scheff, D. A. Price, F. A. Schmitt, S. T. Dekosky, E. J. Mufson

Research output: Contribution to journalArticlepeer-review

623 Scopus citations

Abstract

OBJECTIVE: To evaluate the total number of synapses in the stratum radiatum (str rad) of the human hippocampal CA1 subfield in individuals with mild Alzheimer disease (mAD), mild cognitive impairment (MCI), or no cognitive impairment (NCI) and determine if synapse loss is an early event in the progression of the disease. METHODS: Short postmortem autopsy tissue was obtained, and an unbiased stereologic sampling scheme coupled with transmission electron microscopy was used to directly visualize synaptic contacts. RESULTS: Individuals with mAD had fewer synapses (55%) than the other two diagnostic groups. Individuals with MCI had a mean synaptic value that was 18% lower than the NCI group mean. The total number of synapses showed a correlation with several cognitive tests including those involving both immediate and delayed recall. Total synaptic numbers showed no relationship to the subject's Braak stage or to APOE genotype. The volume of the str rad was reduced in mAD vs the other two diagnostic groups that were not different from each other. CONCLUSION: These results strongly support the concept that synapse loss is a structural correlate involved very early in cognitive decline in mild Alzheimer disease (mAD) and supports mild cognitive impairment as a transitional stage between mAD and no cognitive impairment.

Original languageEnglish
Pages (from-to)1501-1508
Number of pages8
JournalNeurology
Volume68
Issue number18
DOIs
StatePublished - May 2007

ASJC Scopus subject areas

  • Clinical Neurology

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