Sortilin receptor 1 predicts longitudinal cognitive change

NEUROBIOLOGY OF AGING

卷:34

Article

Reynolds, Chandra A.¹  Zavala, Catalina¹  Gatz, Margaret^2,3  Vie, Loryana¹  Johansson, Boo⁴  Malmberg, Bo⁵  Ingelsson, Erik³  Prince, Jonathan A.³  Pedersen, Nancy L.^2,3 

[1] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA

[2] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA

[3] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden

[4] Univ Gothenburg, Dept Psychol, Gothenburg, Sweden

[5] Jonkoping Univ, Sch Hlth Sci, Inst Gerontol, Jonkoping, Sweden

关键词: Cognitive decline;    SORL1 association;    Sortilin receptor 1;    SNP set risk scores;    Sex differences;    Aging;   

DOI  :  10.1016/j.neurobiolaging.2012.12.006

来源: Elsevier

【 摘 要 】

The gene encoding sortilin receptor 1 (SORL1) has been associated with Alzheimer's disease risk. We examined 15 SORL1 variants and single nucleotide polymorphism (SNP) set risk scores in relation to longitudinal verbal, spatial, memory, and perceptual speed performance, testing for age trends and sex-specific effects. Altogether, 1609 individuals from 3 population-based Swedish twin studies were assessed up to 5 times across 16 years. Controlling for apolipoprotein E genotype (APOE), multiple simple and sex-moderated associations were observed for spatial, episodic memory, and verbal trajectories (p = 1.25E-03 to p = 4.83E-02). Five variants (rs11600875, rs753780, rs7105365, rs11820794, rs2070045) were associated across domains. Notably, in those homozygous for the rs2070045 risk allele, men demonstrated initially favorable performance but accelerating declines, and women showed overall lower performance. SNP set risk scores predicted spatial (Card Rotations, p = 5.92E-03) and episodic memory trajectories (Thurstone Picture Memory, p = 3.34E-02), where higher risk scores benefited men's versus women's performance up to age 75 but with accelerating declines. SORL1 is associated with cognitive aging, and might contribute differentially to change in men and women. (C) 2013 Elsevier Inc. All rights reserved.

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