title: Sortilin receptor 1 predicts longitudinal cognitive change.
abstract: 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.
authors: Department of Psychology, University of California, Riverside, CA 92521, USA. chandra.reynolds@ucr.edu
authors: Chandra A
authors: CA
authors: Reynolds
authors: Catalina
authors: C
authors: Zavala
authors: Margaret
authors: M
authors: Gatz
authors: Loryana
authors: L
authors: Vie
authors: Boo
authors: B
authors: Johansson
authors: Bo
authors: B
authors: Malmberg
authors: Erik
authors: E
authors: Ingelsson
authors: Jonathan A
authors: JA
authors: Prince
authors: Nancy L
authors: NL
authors: Pedersen
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D011237:Predictive Value of Tests; D012042:Registries; D012727:Sex Characteristics; D013548:Sweden / Q000453:epidemiology; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000099183:Sortilin