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[P1–141]: EXPLORING APOE GENOTYPE EFFECTS ON AD RISK AND BETA‐AMYLOID BURDEN IN INDIVIDUALS WITH SUBJECTIVE COGNITIVE DECLINE: THE FACEHBI STUDY RESULTS
Author(s) -
MorenoGrau Sonia,
Rodriguez Octavio,
Sanabria Angela,
Perez Alba,
Sanchez Domingo,
Abdelnour Carla,
Valero Sergi,
Hernandez Isabel,
RosendeRoca Maitee,
Mauleon Ana,
Vargas Liliana,
Alegret Monserrat,
Espinosa Ana,
Ortega Gemma,
Guitart Marina,
Gailhajanet Anna,
Rojas Itziar,
SotolongoGrau Oscar,
Ruiz Susana,
Tarragona Marina,
Serra Judit,
Martín Elvira,
Peleja Esther,
Lomeña Francisco,
Campos Francisco,
Vivas Assumpta,
Tejero Miguel Angel,
Giménez Joan,
Pesini Pedro,
Sarasa Manuel,
Martinez Gabriel,
Chiari Marta Gómez,
Orellana Adelina,
Tarraga Lluis,
Ruiz Agustín,
Boada Mercè
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.208
Subject(s) - apolipoprotein e , oncology , medicine , biomarker , neuropathology , amyloid (mycology) , amyloid beta , disease , pathology , genetics , biology
Rotterdam Study. Methods:The Rotterdam Study is a populationbased follow-up study including 14926 participants who have been characterized in depth genetically. We constructed weighted genetic risk scores (GRS), first based on 20 genome-wide significant AD risk variants from the IGAP GWAS, second clustering these variants within the seven genetic pathways. GRS were constructed with and without apolipoprotein E (APOE). We used the Rotterdam Study to investigate the association of the pathway-specific GRS with AD (N1⁄4 1231 cases, 5118 controls), MCI (N1⁄4 360 cases, 3254 controls) and brain MRI phenotypes including white matter lesions, hippocampal volume and brain volume (N 1⁄4 4527 cognitively normal subjects). This was done via regression analyses adjusting for age and sex. Results:AD was significantly associated to overall GRS both with (P1⁄4 1.58*10) and without APOE (P1⁄4 2.23*10). Using pathway-specific GRS, AD was significantly associated with risk scores capturing specifically immune response (P 1⁄4 3.60*10), endocytosis (P 1⁄4 1.2*10) and nominally associated with clathrin/AP2 adaptor complex (P1⁄4 0.04). Studying early pathology, the GRS capturing Immune response (P 1⁄4 0.016) and clathrin/AP2 adaptor complex pathway (P 1⁄4 3.5*10; excluding APOE) were associated to white matter pathology. The endocytosis pathway was associated to MCI (P 1⁄4 1.44*10). Conclusions:Our study suggests that the clinical spectrum of early AD pathology is explained by different genetically driven pathways that are independent of APOE. In particular, the immune response, endocytosis and clathrin/AP2 adaptor complex pathways appear to play a role in the association of vascular pathology and AD.