Presenilin-1 C410Y Alzheimer disease plaques contain synaptic proteins.
Presenilin-1 (PS-1) mutations are associated with familial Alzheimer's disease (AD). Although beta-amyloid (Abeta) plaques in brain tissue are characteristic of AD patients, space occupying "cotton-wool" plaques (CWPs) lacking dense Abeta cores have also been described in patients with mutations in exon 9 of the PS-1 gene. The composition of CWPs has not been fully described. To better elucidate the composition of these space-occupying plaques, we used immunohistochemistry with antibodies to the synaptic proteins synapsin-1 and synaptophysin, as well as antibodies to tau, Abeta(-42), Abeta(-40), ubiquitin, neurofilament, and glial fibrillary acidic protein. Confocal laser scanning microscopy (CLSM) was utilized to further characterize these plaques. CWPs showed increased synapsin-1 and synaptophysin immunoreactivity relative to the background gray matter. Synaptic protein-containing CWPs occurred in all affected MTL regions, including the granule cell layer of the dentate gyrus, where synaptic terminals are usually sparse. These data suggest that in C410Y PS-1 AD patients, CWPs may constitute a major component of synaptic terminal-specific proteins, and that the C410Y PS-1 mutation may influence either synaptic structure or synaptic protein expression.
Haleem
Kamran
K
Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.
Lippa
Carol F
CF
Smith
Thomas W
TW
Kowa
Hisatomo
H
Wu
Jianlin
J
Iwatsubo
Takeshi
T
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009154:Mutation; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics*; D016704:Synapsins / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism*
D053764:Presenilin-1; D016704:Synapsins; D016708:Synaptophysin