Plasma 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 (Aβ ) relate to preclinical markers of neurodegeneration and risk of dementia. We investigated the association of plasma Aβ , Aβ , and Aβ levels with imaging markers of neurodegeneration and risk of dementia in a prospective population-based study. We 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. A 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 Aβ , Aβ , and Aβ (in pg/ml) were 19.4 ± 4.3, 186.1 ± 35.9, and 56.3 ± 6.2, respectively, at baseline. Lower plasma Aβ levels were associated with smaller hippocampal volume (mean difference in hippocampal volume per SD decrease in Aβ 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 Aβ and Aβ were associated with increased risk of dementia, specifically AD (HR for AD per SD decrease in Aβ levels, 1.39; 95% CI, 1.00-2.16; HR for AD per SD decrease in Aβ 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. Our results show that lower plasma Aβ levels were associated with risk of dementia and incident AD. Moreover, lower plasma Aβ levels were related to smaller hippocampal volume. These results suggest that plasma Aβ and Aβ maybe useful biomarkers for identification of individuals at risk of dementia.