TY - JOUR
T1 - Genetic risk for Alzheimer disease in children
T2 - Evidence from early-life IQ and brain white-matter microstructure
AU - Vinueza-Veloz, María Fernanda
AU - Martín-Román, Carlos
AU - Robalino-Valdivieso, María Paulina
AU - White, Tonya
AU - Kushner, Steven A
AU - De Zeeuw, Chris I
N1 - © 2020 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.
PY - 2020
Y1 - 2020
N2 - It remains unclear whether the genetic risk for late-onset Alzheimer disease (AD) is linked to premorbid individual differences in general cognitive ability and brain structure. The objective of the present study was to determine whether the genetic risk of late-onset AD is related to premorbid individual differences in intelligence quotient (IQ) and characteristics of the cerebral white-matter in children. The study sample included children of the Generation R Study from Rotterdam, The Netherlands. IQ was measured using a well-validated Dutch nonverbal IQ test (n = 1908) at ages 5 to 9 years. White-matter microstructure was assessed by measuring fractional anisotropy (FA) of white-matter tracts using diffusion tensor imaging (DTI) (n = 919) at ages 9 to 12 years. Genetic risk was quantified using three biologically defined genetic risk scores (GRSs) hypothesized to be related to the pathophysiology of late-onset AD: immune response, cholesterol/lipid metabolism and endocytosis. Higher genetic risk for late-onset AD that included genes associated with immune responsivity had a negative influence on cognition and cerebral white-matter microstructure. For each unit increase in the immune response GRS, IQ decreased by 0.259 SD (95% CI [-0.500, -0.017]). For each unit increase in the immune response GRS, global FA decreased by 0.373 SD (95% CI [-0.721, -0.026]). Neither cholesterol/lipid metabolism nor endocytosis GRSs were associated with IQ or cerebral white-matter microstructure. Our findings suggest that elevated genetic risk for late-onset AD may in part be manifest during childhood neurodevelopment through alterations in immune responsivity.
AB - It remains unclear whether the genetic risk for late-onset Alzheimer disease (AD) is linked to premorbid individual differences in general cognitive ability and brain structure. The objective of the present study was to determine whether the genetic risk of late-onset AD is related to premorbid individual differences in intelligence quotient (IQ) and characteristics of the cerebral white-matter in children. The study sample included children of the Generation R Study from Rotterdam, The Netherlands. IQ was measured using a well-validated Dutch nonverbal IQ test (n = 1908) at ages 5 to 9 years. White-matter microstructure was assessed by measuring fractional anisotropy (FA) of white-matter tracts using diffusion tensor imaging (DTI) (n = 919) at ages 9 to 12 years. Genetic risk was quantified using three biologically defined genetic risk scores (GRSs) hypothesized to be related to the pathophysiology of late-onset AD: immune response, cholesterol/lipid metabolism and endocytosis. Higher genetic risk for late-onset AD that included genes associated with immune responsivity had a negative influence on cognition and cerebral white-matter microstructure. For each unit increase in the immune response GRS, IQ decreased by 0.259 SD (95% CI [-0.500, -0.017]). For each unit increase in the immune response GRS, global FA decreased by 0.373 SD (95% CI [-0.721, -0.026]). Neither cholesterol/lipid metabolism nor endocytosis GRSs were associated with IQ or cerebral white-matter microstructure. Our findings suggest that elevated genetic risk for late-onset AD may in part be manifest during childhood neurodevelopment through alterations in immune responsivity.
U2 - 10.1111/gbb.12656
DO - 10.1111/gbb.12656
M3 - Article
C2 - 32383552
VL - 19
JO - Genes, Brain and Behavior
JF - Genes, Brain and Behavior
SN - 1601-1848
M1 - e12656
ER -