Association of Apolipoprotein e ϵ4 Allele with Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults with down Syndrome

Altres ajuts: Alzheimer's Strategic Fund; EU Joint Program for Neurodegenerative Disorders; Fundació "La Caixa"; Fundació Catalana Síndrome de Down and Fundació Víctor Grífols i Lucas; Marie Skłodowska-Curie (860197); Sisley D'Ornano Foundations (CM19/00017); Swedish State Support for Clinical Research (201809-2016862); Swedish government (ALFGBG-715986, JPND2019-466-236); National Institutes of Health (1R01AG056850-01A1, R01AG061566, R21AG056974); Alzheimer's Drug Discovery Foundation (ADSF-21-831376-C, ADSF-21-831377-C, ADSF-21-831381-C); Lowe Syndrome Association; Familjen Erling-Perssons Stiftelse (FO2019-0228); Fundació la Marató de TV3 (044412, 20141210); Stiftelsen för Gamla Tjänarinnor; Global Brain Health Institute (1913 Cycle 2019B); Medical Research Council (18HLT09); National Institute for Health Research; Health Foundation; Fondation Jérôme Lejeune; Alzheimer's Research UK; Hjärnfonden; Vetenskapsrådet (681712); European Regional Development Fund (FEDER); Alzheimerfonden (FO2017-0243); Collaboration for Leadership in Applied Health Research and Care - Greater Manchester; NIHR Collaboration for Leadership in Applied Health Research and Care South London ; UK Dementia Research Institute (2017-00915, AF-742881, RDAPB-201809-2016615) Importance: Alzheimer disease (AD) is the leading cause of death in individuals with Down syndrome (DS). Previous studies have suggested that the APOE ϵ4 allele plays a role in the risk and age at onset of dementia in DS; however, data on in vivo biomarkers remain scarce. Objective: To investigate the association of the APOE ϵ4 allele with clinical and multimodal biomarkers of AD in adults with DS. Design, Setting, and Participants: This dual-center cohort study recruited adults with DS in Barcelona, Spain, and in Cambridge, UK, between June 1, 2009, and February 28, 2020. Included individuals had been genotyped for APOE and had at least 1 clinical or AD biomarker measurement; 2 individuals were excluded because of the absence of trisomy 21. Participants were either APOE ϵ4 allele carriers or noncarriers. Main Outcomes and Measures: Participants underwent a neurological and neuropsychological assessment. A subset of participants had biomarker measurements: Aβ1-42, Aβ1-40, phosphorylated tau 181 (pTau181) and neurofilament light chain (NfL) in cerebrospinal fluid (CSF), pTau181, and NfL in plasma; amyloid positron emission tomography (PET); fluorine 18-labeled-fluorodeoxyglucose PET; and/or magnetic resonance imaging.