N Schupf1, W B Zigman, M-X Tang, D Pang, R Mayeux, P Mehta, W Silverman. 1. Taub Institute for Research on AD and the Aging Brain, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA. ns24@columbia.edu
Abstract
OBJECTIVE: To examine changes in levels of plasma amyloid-β (Aβ) peptides, Aβ42 and Aβ40, in relation to onset of Alzheimer disease (AD) in adults with Down syndrome (DS). METHODS: Plasma Aβ42 and Aβ40 were measured at initial examination and at follow-up in a community-based cohort of 225 adults with DS who did not have dementia at baseline and were assessed for cognitive/functional abilities and health status and followed at 14- to 20-month intervals. We used Cox proportional hazards modeling to estimate the cumulative incidence of AD by Aβ peptide change group (increasing, no change, or decreasing), adjusting for covariates. RESULTS: Sixty-one (27.1%) of the participants developed AD. At follow-up, a decrease in Aβ42 levels, a decrease in the Aβ42/Aβ40 ratio, and an increase in Aβ40 levels were related to conversion to AD. Compared with the group with increasing levels of Aβ42, the likelihood of developing AD was 5 times higher for those whose plasma Aβ42 levels decreased over follow-up (hazard ratio [HR] = 4.9, 95% confidence interval [CI] 2.1-11.4). Decreasing Aβ42/Aβ40 was also strongly related to AD risk (HR = 4.9, 95% CI 1.8-13.2), while decreasing Aβ40 was associated with lower risk (HR = 0.4, 95% CI 0.2-0.9). CONCLUSIONS: Among adults with DS, decreasing levels of plasma Aβ42, a decline in the Aβ42/Aβ40 ratio, or increasing levels of Aβ40 may be sensitive indicators of conversion to AD, possibly reflecting compartmentalization of Aβ peptides in the brain.
OBJECTIVE: To examine changes in levels of plasma amyloid-β (Aβ) peptides, Aβ42 and Aβ40, in relation to onset of Alzheimer disease (AD) in adults with Down syndrome (DS). METHODS: Plasma Aβ42 and Aβ40 were measured at initial examination and at follow-up in a community-based cohort of 225 adults with DS who did not have dementia at baseline and were assessed for cognitive/functional abilities and health status and followed at 14- to 20-month intervals. We used Cox proportional hazards modeling to estimate the cumulative incidence of AD by Aβ peptide change group (increasing, no change, or decreasing), adjusting for covariates. RESULTS: Sixty-one (27.1%) of the participants developed AD. At follow-up, a decrease in Aβ42 levels, a decrease in the Aβ42/Aβ40 ratio, and an increase in Aβ40 levels were related to conversion to AD. Compared with the group with increasing levels of Aβ42, the likelihood of developing AD was 5 times higher for those whose plasma Aβ42 levels decreased over follow-up (hazard ratio [HR] = 4.9, 95% confidence interval [CI] 2.1-11.4). Decreasing Aβ42/Aβ40 was also strongly related to AD risk (HR = 4.9, 95% CI 1.8-13.2), while decreasing Aβ40 was associated with lower risk (HR = 0.4, 95% CI 0.2-0.9). CONCLUSIONS: Among adults with DS, decreasing levels of plasma Aβ42, a decline in the Aβ42/Aβ40 ratio, or increasing levels of Aβ40 may be sensitive indicators of conversion to AD, possibly reflecting compartmentalization of Aβ peptides in the brain.
Authors: B Rumble; R Retallack; C Hilbich; G Simms; G Multhaup; R Martins; A Hockey; P Montgomery; K Beyreuther; C L Masters Journal: N Engl J Med Date: 1989-06-01 Impact factor: 91.245
Authors: Wayne Silverman; Nicole Schupf; Warren Zigman; Darlynne Devenny; Charles Miezejeski; Romaine Schubert; Robert Ryan Journal: Am J Ment Retard Date: 2004-03
Authors: A Assini; S Cammarata; A Vitali; M Colucci; L Giliberto; R Borghi; M L Inglese; S Volpe; S Ratto; F Dagna-Bricarelli; C Baldo; A Argusti; P Odetti; A Piccini; M Tabaton Journal: Neurology Date: 2004-09-14 Impact factor: 9.910
Authors: Giovanna Cenini; Amy L S Dowling; Tina L Beckett; Eugenio Barone; Cesare Mancuso; Michael Paul Murphy; Harry Levine; Ira T Lott; Frederick A Schmitt; D Allan Butterfield; Elizabeth Head Journal: Biochim Biophys Acta Date: 2011-10-08
Authors: Jon B Toledo; Hugo Vanderstichele; Michal Figurski; Paul S Aisen; Ronald C Petersen; Michael W Weiner; Clifford R Jack; William Jagust; Charles Decarli; Arthur W Toga; Estefanía Toledo; Sharon X Xie; Virginia M-Y Lee; John Q Trojanowski; Leslie M Shaw Journal: Acta Neuropathol Date: 2011-07-30 Impact factor: 17.088
Authors: Eric D Hamlett; Edward J Goetzl; Aurélie Ledreux; Vitaly Vasilevko; Heather A Boger; Angela LaRosa; David Clark; Steven L Carroll; María Carmona-Iragui; Juan Fortea; Elliott J Mufson; Marwan Sabbagh; Abdul H Mohammed; Dean Hartley; Eric Doran; Ira T Lott; Ann-Charlotte Granholm Journal: Alzheimers Dement Date: 2016-10-15 Impact factor: 21.566
Authors: Sylvia E Perez; Jennifer C Miguel; Bin He; Michael Malek-Ahmadi; Eric E Abrahamson; Milos D Ikonomovic; Ira Lott; Eric Doran; Melissa J Alldred; Stephen D Ginsberg; Elliott J Mufson Journal: Acta Neuropathol Date: 2019-02-07 Impact factor: 17.088
Authors: Michael S Rafii; Beau M Ances; Nicole Schupf; Sharon J Krinsky-McHale; Mark Mapstone; Wayne Silverman; Ira Lott; William Klunk; Elizabeth Head; Brad Christian; Florence Lai; H Diana Rosas; Shahid Zaman; Melissa E Petersen; Andre Strydom; Juan Fortea; Benjamin Handen; Sid O'Bryant Journal: Alzheimers Dement (Amst) Date: 2020-10-27