Relationship of phosphorylated alpha-synuclein and tau accumulation to Abeta deposition in the cerebral cortex of dementia with Lewy bodies.
Alpha-synuclein accumulated in the brain of dementia with Lewy bodies (DLB) is phosphorylated at serine129 (palpha-synuclein). We investigated the accumulation of palpha-synuclein in the brains of patients with DLB and Alzheimer's disease (AD). We employed 18 DLB patients with neocortical Lewy body type pathology (nLBTP) with or without AD. We also employed the same number of AD cases without significant nLBTP. We refer to the former group as the nLBTP group and to the latter as the AD type pathology (ADTP) group. In the nLBTP group, palpha-synuclein positive neurite pathology such as threads and dots occurs in all layers of the temporal neocortex. It was comparable in degree with tau pathology in AD. Fifteen cases in the nLBTP group were associated with Abeta deposition that meets the CERAD plaque score "C" and one case with a score "B". In these plaque-associated cases, the severity of palpha-synuclein pathology was related to the degree of Abeta deposition. In the cases with relatively moderate Abeta deposition, tau pathology was disproportionately mild in the nLBTP group, while the total of tau and palpha-synuclein pathology was proportionate to Abeta deposition in both the nLBTP and ADTP groups. Our results support the ideas that there is an overlap in the pathology between AD and DLB and that Abeta promotes accumulation of both alpha-synuclein and tau. The procession from Abeta to neurite pathology in the cerebral cortex of AD and DLB may be unifiable.
Obi
Kimiko
K
Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Akiyama
Haruhiko
H
Kondo
Hiromi
H
Shimomura
Yoko
Y
Hasegawa
Masato
M
Iwatsubo
Takeshi
T
Mizuno
Yoshikuni
Y
Mochizuki
Hideki
H
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D020961:Lewy Body Disease / Q000473:pathology*; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D008875:Middle Aged; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012694:Serine / Q000378:metabolism; D018709:Statistics, Nonparametric; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins; D012694:Serine