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A Prospective, Population-Based Cohort Study

Johan Sundelöf, MD; Vilmantas Giedraitis, PhD; Michael C. Irizarry, MD; Johan Sundström, MD, PhD; Erik Ingelsson, MD, PhD; Elina Rönnemaa, MD; Johan Ärnlöv, MD, PhD; Malin Degerman Gunnarsson, MD; Bradley T. Hyman, MD, PhD; Hans Basun, MD, PhD; Martin Ingelsson, MD, PhD; Lars Lannfelt, MD, PhD; Lena Kilander, MD, PhD

Arch Neurol. 2008;65(2):256-263.

Background  β Amyloid (Aβ) protein accumulates in the brains of individuals with Alzheimer disease (AD) and is detectable in cerebrospinal fluid and plasma.

Objective  To examine plasma levels of Aβ peptides Aβ₄₀ and Aβ₄₂ as predictors of incident AD and other types of dementia.

Design  Prospective, population-based cohort study.

Setting  The Uppsala Longitudinal Study of Adult Men.

Participants  Plasma Aβ₄₀ and Aβ₄₂ levels were analyzed as predictors of incident AD in 1045 men at age 70 years and 680 men at age 77 years using Cox proportional hazards analyses. Alzheimer disease and other types of dementia were diagnosed by standardized screening, clinical evaluation, and medical record review.

Main Outcome Measures  Hazard ratios of AD (primary outcome) and vascular dementia or other dementia (secondary outcomes) according to baseline levels of plasma Aβ₄₀ and Aβ₄₂.

Results  From the age of 77 years at baseline, 46 individuals developed AD at follow-up (median, 5.3 years). A low plasma Aβ₄₀ level at age 77 years was associated with higher incidence of AD. The multivariate-adjusted hazard ratio was 4.87 (95% confidence interval, 1.63-14.6) for the lowest Aβ₄₀ tertile compared with the highest tertile. On follow-up from age 70 years at baseline (median, 11.2 years), 82 individuals developed AD. Plasma Aβ₄₀ and Aβ₄₂ levels measured at age 70 years were not significantly associated with incident AD.

Conclusions  Low plasma Aβ₄₀ levels predicted incident AD in elderly men independently of potential confounders. Plasma Aβ₄₂ levels were not significantly associated with AD incidence. The clinical value of Aβ measurement in plasma remains to be established in future studies.

Author Affiliations: Departments of Public Health and Geriatrics (Drs Sundelöf, Giedraitis, E. Ingelsson, Rönnemaa, Ärnlöv, Gunnarsson, Basun, M. Ingelsson, Lannfelt, and Kilander) and Medical Sciences (Dr Sundström), Uppsala University, Uppsala, Sweden; Massachusetts General Hospital, Boston (Drs Irizarry and Hyman); and AstraZeneca, Södertälje, Sweden (Dr Basun). Dr Irizarry is now affiliated with WW Epidemiology, GlaxoSmithKline, Research Triangle Park, North Carolina.

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