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


CONCLUSIONS
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.
Scheff
S W
SW
Sanders-Brown Center on Aging and Alzheimer Disease Research Center, University of Kentucky College of Medicine, Lexington, KY 40536-0230, USA. sscheff@email.uky.edu
Price
D A
DA
Schmitt
F A
FA
DeKosky
S T
ST
Mufson
E J
EJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology; D049229:Dendritic Spines / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D017729:Presynaptic Terminals / Q000473:pathology; D011379:Prognosis; D013569:Synapses / Q000473:pathology*