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The objective of the present study was to determine whether the genetic risk of late\u2010onset AD is related to premorbid individual differences in intelligence quotient (IQ) and characteristics of the cerebral white\u2010matter in children. The study sample included children of the Generation R Study from Rotterdam, The Netherlands. IQ was measured using a well\u2010validated Dutch nonverbal IQ test (n = 1908) at ages 5 to 9\u2009years. White\u2010matter microstructure was assessed by measuring fractional anisotropy (FA) of white\u2010matter tracts using diffusion tensor imaging (DTI) (n = 919) at ages 9 to 12\u2009years. Genetic risk was quantified using three biologically defined genetic risk scores (GRSs) hypothesized to be related to the pathophysiology of late\u2010onset AD: immune response, cholesterol\/lipid metabolism and endocytosis. Higher genetic risk for late\u2010onset AD that included genes associated with immune responsivity had a negative influence on cognition and cerebral white\u2010matter microstructure. For each unit increase in the immune response GRS, IQ decreased by 0.259 SD (95% CI [\u22120.500, \u22120.017]). For each unit increase in the immune response GRS, global FA decreased by 0.373 SD (95% CI [\u22120.721, \u22120.026]). Neither cholesterol\/lipid metabolism nor endocytosis GRSs were associated with IQ or cerebral white\u2010matter microstructure. Our findings suggest that elevated genetic risk for late\u2010onset AD may in part be manifest during childhood neurodevelopment through alterations in immune responsivity.<\/jats:p>","DOI":"10.1111\/gbb.12656","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T09:14:59Z","timestamp":1588929299000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genetic risk for Alzheimer disease in children: Evidence from early\u2010life IQ and brain white\u2010matter microstructure"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2493-0769","authenticated-orcid":false,"given":"Mar\u00eda Fernanda","family":"Vinueza\u2010Veloz","sequence":"first","affiliation":[{"name":"School of Medicine, Escuela Superior Polit\u00e9cnica de Chimborazo Riobamba Ecuador"},{"name":"Department of Neuroscience Erasmus MC Rotterdam The 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Psychiatry Erasmus MC Rotterdam The Netherlands"},{"name":"Department of Psychiatry Columbia University New York City, United States of America United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris I.","family":"De Zeeuw","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Erasmus MC Rotterdam The Netherlands"},{"name":"Royal Netherlands Academy of Arts and Sciences The Netherlands Institute for Neuroscience Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,8]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Global Burden of Dementia in the Year 2000: Summary of Methods and Data Sources","author":"Colin M","year":"2000"},{"key":"e_1_2_8_3_1","article-title":"Alzheimer disease","author":"Shaheen 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