Elevated plasma beta-amyloid peptide Abeta(42) levels, incident dementia, and mortality in Down syndrome.
BACKGROUND
Deposition of the beta-amyloid peptide Abeta(42) is thought to be an important initial step in the pathogenesis of Alzheimer disease (AD). Individuals with Down syndrome have increased levels of beta-amyloid peptides and an increased risk for AD.


OBJECTIVE
To examine the relation of plasma levels of Abeta(42) and Abeta(40) to the risk of dementia in nondemented participants and all-cause mortality in adults with Down syndrome.


METHODS
Prospective, community-based longitudinal cohort study.


METHODS
State and voluntary service providers in New York State.


METHODS
Adults with Down syndrome (N = 204).


METHODS
Plasma Abeta(42) and Abeta(40) levels were measured at initial examination. Participants were assessed for cognitive and functional abilities, behavioral/psychiatric conditions, and health and vital status at 14- to 18-month intervals for 4 cycles of data collection.


RESULTS
Among participants who were nondemented at baseline, those in the middle and highest tertiles of plasma Abeta(42) levels were more than 2 times as likely to develop AD as those in the lowest tertile. Compared with participants without AD, participants with prevalent AD had higher levels of plasma Abeta(42) but not Abeta(40). Among all participants, those in the highest tertile of plasma Abeta(42) level at baseline were more than twice as likely to die during the study period as those in the lowest tertile, whereas there was no difference in risk of death between those in the middle and lowest tertiles of plasma Abeta(42) level.


CONCLUSIONS
Elevations in plasma Abeta(42) peptide levels are associated with earlier onset of AD and increased risk of death.
Schupf
Nicole
N
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, PO Box 16, 630 W 168th St, New York, NY 10032, USA. ns24@columbia.edu
Patel
Bindu
B
Pang
Deborah
D
Zigman
Warren B
WB
Silverman
Wayne
W
Mehta
Pankaj D
PD
Mayeux
Richard
R
D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000097:blood*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001921:Brain / Q000503:physiopathology*; D015897:Comorbidity; D004314:Down Syndrome / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D005260:Female; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009518:New York / Q000453:epidemiology; D010446:Peptide Fragments / Q000032:analysis / Q000097:blood*; D011237:Predictive Value of Tests; D012307:Risk Factors; D015854:Up-Regulation / Q000502:physiology
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)