Elevated plasma amyloid beta-peptide 1-42 and onset of dementia in adults with Down syndrome.
We compared levels of plasma amyloid beta-peptides Abeta1-42 and Abeta1-40 in 108 demented and nondemented adults with Down syndrome (DS) and 64 adults from the general population. Abeta1-42 and Abeta1-40 levels were significantly higher in adults with DS than in controls (P=0.0001). Compared to nondemented adults with DS, Abeta1-42 levels in demented adults with DS were selectively increased by 26% (28.2 pg/ml vs. 22.4 pg/ml, P=0.004). In addition, mean plasma levels of Abeta1-42 were 22% higher in DS cases with the apolipoprotein varepsilon4 allele than in DS subjects without an varepsilon4 allele (25.9 pg/ml vs. 21.2 pg/ml, P=0.01), while mean plasma levels of Abeta1-40 did not vary by APOE genotype. These results support the hypothesis that Abeta1-42 plays an important role in the pathogenesis of dementia associated with DS, as it does in Alzheimer's disease, and that variations in plasma levels may be related to disease progression.
Department of Psychology and Laboratory of Epidemiology, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. ns24@columbia.edu
N
N
Schupf
B
B
Patel
W
W
Silverman
W B
WB
Zigman
N
N
Zhong
B
B
Tycko
P D
PD
Mehta
R
R
Mayeux
D000328:Adult; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000097:blood*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D018450:Disease Progression; D004314:Down Syndrome / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)