Cerebrovascular smooth muscle actin is increased in nondemented subjects with frequent senile plaques at autopsy: implications for the pathogenesis of Alzheimer disease.
We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared with brains of nondemented, neuropathologically normal subjects. To assess the pathogenetic significance and disease specificity of this finding, we studied 3 additional patient groups: nondemented subjects without significant AD type pathology ("Normal"; n = 20), nondemented subjects with frequent senile plaques at autopsy ("Preclinical AD"; n = 20), and subjects with frontotemporal dementia ("FTD"; n = 10). The groups were matched for sex and age with those previously reported; SMA immunohistochemistry and image analysis were performed as previously described. Surprisingly, SMA expression in arachnoid, cerebral cortex, and white matter arterioles was greater in the Preclinical AD group than in the Normal and FTD groups. The plaques were not associated with amyloid angiopathy or other vascular disease in this group. Smooth muscle actin expression in the brains of the Normal group was intermediate between the Preclinical AD and FTD groups. All 3 groups exhibited much greater SMA expression than in our previous report. The presence of frequent plaques and increased arteriolar SMA expression in the brains of nondemented subjects suggest that increased SMA expression might represent a physiological response to neurodegeneration that could prevent or delay overt expression dementia in AD.
Hulette
Christine M
CM
Department of Pathology (Neuropathology), Joseph and Kathleen Price Bryan Alzheimer Disease Research Center, Duke University Medical Center, Durham, NC, USA. hulet001@mc.duke.edu
Ervin
John F
JF
Edmonds
Yvette
Y
Antoine
Samantha
S
Stewart
Nicolas
N
Szymanski
Mari H
MH
Hayden
Kathleen M
KM
Pieper
Carl F
CF
Burke
James R
JR
Welsh-Bohmer
Kathleen A
KA
D000199:Actins / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D001344:Autopsy; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D003072:Cognition Disorders / Q000473:pathology; D003704:Dementia / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000473:pathology*
D000199:Actins