Hippocampal drebrin loss in mild cognitive impairment.
Alterations in the relative abundance of synaptic proteins may contribute to hippocampal synaptic dysfunction in Alzheimer's disease (AD). The extent to which perturbations in synaptic protein expression occur during the earliest stages of cognitive decline remains unclear. We examined protein levels of presynaptic synaptophysin (SYP) and synaptotagmin (SYT), and postsynaptic drebrin (DRB), a marker for dendritic spine plasticity, in the hippocampus of people with an antemortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI) or mild/moderate AD. Although normalized SYP and SYT levels were preserved, DRB was reduced by approximately 40% in the hippocampus of MCI and AD compared to NCI subjects. This differential alteration of synaptic markers in MCI suggests a selective impairment in hippocampal postsynaptic dendritic plasticity in prodromal AD that likely heralds the onset of memory impairment in symptomatic disease.
Department of Neurological Sciences, Rush University Medical Center, Chicago, Ill 60612, USA.
Scott E
SE
Counts
Bin
B
He
Muhammad
M
Nadeem
Joanne
J
Wuu
Stephen W
SW
Scheff
Elliott J
EJ
Mufson
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D060825:Cognitive Dysfunction / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D016708:Synaptophysin / Q000378:metabolism; D050857:Synaptotagmins / Q000378:metabolism
D009479:Neuropeptides; D016708:Synaptophysin; C053386:drebrins; D050857:Synaptotagmins