title: Depression and plasma amyloid beta peptides in the elderly with and without the apolipoprotein E4 allele.
abstract: Depression associated with low plasma amyloid-beta peptide 42 (Abeta42) leading to a high ratio of Abeta40/Abeta42, a biomarker of Alzheimer disease (AD), may represent a unique depression subtype. The relationship between low plasma Abeta42 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 Abeta40 and Abeta42 were measured, and cognition were evaluated. In the absence of the ApoE4 allele, depressed subjects had lower plasma Abeta42 [median (Q1, Q3): 17.1 (11.6, 27.8) vs. 20.2 (12.9, 32.9) pg/mL, P=0.006], a higher Abeta40/Abeta42 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 Abeta42 and a higher Abeta40/Abeta42 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 Abeta42 and ApoE4 (odds ratio=3.94, 95% confidence interval=1.50, 10.33, P=0.005), denoting low plasma Abeta42 in the absence of ApoE4. Both ApoE4 carriers and non-ApoE4 carriers with depression had lower Abeta42 and a higher Abeta40/Abeta42 ratio in plasma compared with non-ApoE4 carriers without depression in the homebound elderly. As a combination of low plasma Abeta42 and high plasma Abeta40 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.
authors.affiliation: Department of Psychiatry, Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sun
authors.forename: Chi Chia
authors.initials: CC
authors.lastname: Chiu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Liebson
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Crivello
authors.forename: Lixia
authors.initials: L
authors.lastname: Wang
authors.forename: Joshua
authors.initials: J
authors.lastname: Claunch
authors.forename: Marshal
authors.initials: M
authors.lastname: Folstein
authors.forename: Irwin
authors.initials: I
authors.lastname: Rosenberg
authors.forename: D Mkaya
authors.initials: DM
authors.lastname: Mwamburi
authors.forename: Inga
authors.initials: I
authors.lastname: Peter
authors.forename: Wei Qiao
authors.initials: WQ
authors.lastname: Qiu
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000097:blood*; D053327:Apolipoprotein E4 / Q000235:genetics*; D003430:Cross-Sectional Studies; D003863:Depression / Q000097:blood* / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D016133:Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)