Depression and Plasma Amyloid β Peptides in the Elderly With and Without the Apolipoprotein E4 Allele

Abstract

Depression associated with low plasma Amyloid-β peptide 42 (Aβ42) leading to a high ratio of Aβ40/Aβ42, a biomarker of Alzheimer's 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 crosssectional 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 MiniMental 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 nonApoE4 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 (OR = 3.94, 95% CI = 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 to non-ApoE4 carriers without depression in the homebound elderly. Since a combination of low plasma Aβ42 and high plasma Aβ40 has been shown to increase the risk of AD in two large cohort studies, amyloid-associated depression shown in this study may suggest a risk factor of AD in the absence of ApoE4.

Amyloid Hypothesis: Is There a Role for Antiamyloid Treatment in Late-Life Depression?

“…Two cross-sectional studies reported an elevation of plasma Aβ42 in individuals with late-life major depression (25) or depressive symptoms and signs compared to non- depressed subjects (26). However, other cross-sectional studies found an inverse relationship between plasma Aβ42 and depressive symptomatology (27) (28) (29). Depression with high plasma Aβ40/Aβ42 ratio was accompanied by impairment in memory, visuospatial task performance, and executive function (29).…”

Depression and Cognition in the Elderly

“…However, Metti et al (2013) did not find a relationship between plasma Aβ42 levels and depression; they found, however, that a low plasma Aβ42/Aβ40 ratio was associated with an increased risk of incident depression in individuals carrying the APOE ε4 allele, suggesting a complex interaction between depression, Aβ levels, and APOE. Sun et al (2009) found that lower plasma Aβ42 levels and higher Aβ40/Aβ42 ratios were associated with depressed older adults, independent of APOE genotype. Tau proteins are microtubule-associated proteins that are important for axonal transport and cell shape and play a significant role in neurodegenerative disorders.…”

Soluble Amyloid-&#946; . Levels and Late-Life Depression

“…In the presence of CVD, the association disappeared. Subsequent analyses from the same cohort on samples of 324 [76], 995 [78], and 1060 [77] elders (with and without CVD) confirmed the finding that subjects with depression had 13.5% lower median plasma Aβ42 levels and a higher Aβ40/Aβ42 ratio than did those without depression [78]. Another finding from this cohort was that only in the absence of the ApoE4 allele, depressed subjects had significantly lower plasma Aβ42 and a higher Aβ40/Aβ42 ratio than those without depression.…”

“…Another finding from this cohort was that only in the absence of the ApoE4 allele, depressed subjects had significantly lower plasma Aβ42 and a higher Aβ40/Aβ42 ratio than those without depression. When subjects with CVD were excluded from this subset of non-ApoE4 carriers, the differences in plasma Aβ42 concentration in those with and without depression became more significant [77]. Mean age of LLMD subjects in this cohort was 73.8±8.5 years and the sample was comprised of homebound elderly with multiple concomitant chronic diseases.…”