Defining the Genetic Etiology of Alzheimer's Disease in the Faroe Islands

The aim of the study is to unravel genetic and environmental factors that influence the risk and/or susceptibility of AD. Thus, subjects with AD and family members when there is a strong history of AD are being recruited. Data collection includes a blood sample, clinical phenotype data from hospital records, standardized assessment scales (e.g. Geriatric Depression Scale (GDS), Neuropsychiatric Inventory Questionnaire (NPI-Q), Functional Activities Questionnaire (FAQ-IADL), tests of mental function (Mini Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination (ACE)) and family and lifestyle/environmental questionnaire. Furthermore are control subjects being recruited where data includes a blood sample, MMSE and a lifestyle/environmental questionnaire.

Initial genetic analyses will focus on known genetic risk factors for AD by looking at the most highly associated single nucleotide polymorphisms in loci harboring e.g. apolipoprotein E (APOE)/Translocase Of Outer Mitochondrial Membrane 40 (TOMM40), MAPT, Phosphatidylinositol Binding Clathrin Assembly Protein (PICALM). Subsequent analyses will focus on genome-wide array genotyping of ~ 1.8 million markers, e.g. to accommodate the population structure. Finally, patients with a family history of AD who cannot be explained by the before mentioned analysis will be subject to exome sequencing. Exposure analyses will focus on persistant organic pollutants, e.g. polychlorinated biphenyls (PCBs), perfluorinated alkylated substances (PFAS) and also mercury.

The investigators believe the Faroese population presents a unique opportunity to more readily identify genetic and environmental factors involved in AD due to its characteristics as a geographic, environmental and genetic isolate with a homogeneous genetic background.