Genetic risk for Alzheimer disease in children: Evidence from early-life IQ and brain white-matter microstructure
| Autor: | Tonya White, Carlos Martín‐Román, María Paulina Robalino‐Valdivieso, María Fernanda Vinueza-Veloz, Steven A. Kushner, Chris I. De Zeeuw |
|---|---|
| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN), Neurosciences, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Psychiatry |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Intelligence Physiology Snijders Oomen Non‐verbal Intelligence Test brain white‐matter genetic risk score immune response 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Immune system children Alzheimer Disease Fractional anisotropy Genetics medicine Humans endocytosis Genetic Predisposition to Disease Child Intelligence Tests Intelligence quotient business.industry Cholesterol Brain Lipid metabolism Cognition Original Articles Alzheimer's disease cholesterol/lipid metabolism medicine.disease diffusion tensor imaging White Matter 030104 developmental biology Early Diagnosis Neurology chemistry IQ Generation R Female Original Article business 030217 neurology & neurosurgery |
| Zdroj: | Genes, Brain, and Behavior Genes, Brain and Behavior, 19:e12656. Wiley-Blackwell Genes, Brain and Behavior, 19(6):e12656. Wiley-Blackwell Publishing Ltd |
| ISSN: | 1601-183X 1601-1848 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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