Abstract
BackgroundPlasma amyloid-β (Aβ) levels are increasingly studied as a potential accessible marker of cognitive impairment and dementia. However, it remains underexplored whether plasma Aβ levels including the novel Aβ peptide 1–38 (Aβ1–38) relate to preclinical markers of neurodegeneration and risk of dementia. We investigated the association of plasma Aβ1–38, Aβ1–40, and Aβ1–42 levels with imaging markers of neurodegeneration and risk of dementia in a prospective population-based study.MethodsWe analyzed plasma Aβ levels in 458 individuals from the Rotterdam Study. Brain volumes, including gray matter, white matter, and hippocampus, were computed on the basis of 1.5-T magnetic resonance imaging (MRI). Dementia and its subtypes were defined on the basis of internationally accepted criteria.ResultsA total of 458 individuals (mean age, 67.8 ± 7.7 yr; 232 [50.7%] women) with baseline MRI scans and incident dementia were included. The mean ± SD values of Aβ1–38, Aβ1–40, and Aβ1–42 (in pg/ml) were 19.4 ± 4.3, 186.1 ± 35.9, and 56.3 ± 6.2, respectively, at baseline. Lower plasma Aβ1–42 levels were associated with smaller hippocampal volume (mean difference in hippocampal volume per SD decrease in Aβ1–42 levels, − 0.13; 95% CI, − 0.23 to − 0.04; p = 0.007). After a mean follow-up of 14.8 years (SD, 4.9; range, 4.1–23.5 yr), 79 persons developed dementia, 64 of whom were diagnosed with Alzheimer’s disease (AD). Lower levels of Aβ1–38 and Aβ1–42 were associated with increased risk of dementia, specifically AD (HR for AD per SD decrease in Aβ1–38 levels, 1.39; 95% CI, 1.00–2.16; HR for AD per SD decrease in Aβ1–42 levels, 1.35; 95% CI, 1.05–1.75) after adjustment for age, sex, education, cardiovascular risk factors, apolipoprotein E ε4 allele carrier status, and other Aβ isoforms.ConclusionsOur results show that lower plasma Aβ levels were associated with risk of dementia and incident AD. Moreover, lower plasma Aβ1–42 levels were related to smaller hippocampal volume. These results suggest that plasma Aβ1–38 and Aβ1–42 maybe useful biomarkers for identification of individuals at risk of dementia.
Highlights
Plasma amyloid-β (Aβ) levels are increasingly studied as a potential accessible marker of cognitive impairment and dementia
Lower levels of Aβ peptide 1–38 (Aβ1–38) and Aβ1–42 were associated with increased risk of dementia (HR for dementia per SD decrease in Aβ1–38, 1.33; 95% CI, 1.01–1.89; HR for dementia per SD decrease in Aβ1–42, 1.27; 95% CI, 1.02– 1.58) (Table 3)
The association between lower levels of Aβ and risk of dementia among Apolipoprotein E (APOE)-ε4 carriers and noncarriers appeared similar, such that lower levels of Aβ1–38, Aβ1–40, and Aβ1–42 were associated with increased risk of dementia in both strata
Summary
Plasma amyloid-β (Aβ) levels are increasingly studied as a potential accessible marker of cognitive impairment and dementia. It remains underexplored whether plasma Aβ levels including the novel Aβ peptide 1–38 (Aβ1–38) relate to preclinical markers of neurodegeneration and risk of dementia. We investigated the association of plasma Aβ1–38, Aβ1–40, and Aβ1–42 levels with imaging markers of neurodegeneration and risk of dementia in a prospective population-based study. Several large community-based studies have reported on the association of high plasma Aβ1–40 and Aβ1–42 levels and lower Aβ1–42/Aβ1–40 ratios at baseline with risk of dementia and reduced cognitive measure scores [5,6,7]. More studies of a general population are needed to investigate the relationship between Aβ and markers of neurodegeneration as well as risk of dementia to further comprehend the underlying mechanisms in a subclinical phase
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