Depression and plasma amyloid β peptides in the elderly with and without the apolipoprotein E4 allele

Depression associated with low plasma amyloid-β peptide 42 (Aβ42) leading to a high ratio of Aβ40/Aβ42, a biomarker of Alzheimer disease (AD), may represent a unique depression subtype. The relationship between low plasma Aβ42 in depression and the major risk factor of AD, apolipoprotein E4 (ApoE4), is unknown. With the goal of clarifying this relationship, we analyzed 1060 homebound elders with ApoE characterization and depression status in a cross-sectional study. Plasma Aβ40 and Aβ42 were measured, and cognition were evaluated. In the absence of the ApoE4 allele, depressed subjects had lower plasma Aβ42 [median (Q1, Q3): 17.1 (11.6, 27.8) vs. 20.2 (12.9, 32.9) pg/mL, P=0.006], a higher Aβ40/Aβ42 ratio [median (Q1, Q3): 7.1 (4.6, 11.3) vs. 6.9 (3.4, 9.7), P=0.03], and lower cognitive function (mean±SD of Mini-Mental State Examination: 24.5±3.1 vs. 25.5±3.3, P<0.0001) than those without depression. In contrast, these relationships were not observed in the presence of ApoE4. Instead, regardless the depression status ApoE4 carriers had lower plasma Aβ42 and a higher Aβ40/Aβ42 ratio than non-ApoE4 carriers. Using multivariate logistic regression, it was found that depression was not associated with ApoE4 allele, but with the interaction between plasma Aβ42 and ApoE4 (odds ratio=3.94, 95% confidence interval=1.50, 10.33, P=0.005), denoting low plasma Aβ42 in the absence of ApoE4. Both ApoE4 carriers and non-ApoE4 carriers with depression had lower Aβ42 and a higher Aβ40/Aβ42 ratio in plasma compared with non-ApoE4 carriers without depression in the homebound elderly. As a combination of low plasma Aβ42 and high plasma Aβ40 has been shown to increase the risk of AD in 2 large cohort studies, amyloid-associated depression shown in this study may suggest a risk factor of AD in the absence of ApoE4.