A strong link is indicated between cardiovascular disease (CVD) and risk for developing Alzheimer’s disease (AD),which may be exacerbated by the majorADgenetic risk factor apolipoprotein Eε4 (APOEε4). Since subjective memory complaint(SMC) may potentially be an early indicator for cognitive decline, we examined CVD risk factors in a cohort of SMC. Asamyloid-β (Aβ) is considered to play a central role in AD, we hypothesized that the CVD risk profile (increased LDL, reducedHDL, and increased body fat) would be associated with plasma Aβ levels. We explored this in 198 individuals with and withoutSMC (average age = 63 years). Correlations between Aβ40 and HDL were observed, which were stronger in non-APOEε4carriers (rho = −0.315, p <0.001) and in SMC (rho = −0.322, p = 0.01). There was no relationship between percentage bodyfat and Aβ40 in this cohort. Age and HDL remained predictive for plasma Aβ40 using multivariate regression analysis. We reporta novel negative association between HDL and Aβ, which if demonstrated to be causal has implications for the development oflifestyle interventions and/or novel therapeutics. The relationship between HDL and Aβ and the potential significance of suchan association needs to be validated in a larger longitudinal study.