Complex phenotypic analysis to identify genes which contribute to or modify the development of Alzheimer's disease

摘要: Late-onset Alzheimer's disease (LOAD) is a heritable disorder. It invariably characterised by decline in cognitive abilities, however, marked variation behavioural symptoms and age at onset are observed between sufferers. This clinical heterogeneity may be genetically modified, hence, provide productive avenue of exploration for those seeking to unravel the genetic aetiology LOAD. thesis employed sequential three stage approach search loci implicated development influenced features disease. Behavioural 1,120 unrelated individuals with LOAD were assessed using Neuropsychiatric Inventory. The 12 symptom domain scores subjected principal components analysis. Three interpretable identified, comprising: "frontal lobe dysfunction", "psychosis" "mood". These remained stable when taking account severity. familiality was assessed. Affected siblings from 388 families terms aggression, psychosis mood disturbances. Age data available affected 458 families. Familial clustering found onset, psychosis, aggression mild depression, strongest evidence noted psychosis. Major depression combined phenotype anxiety showed limited familial aggregation. Covariate linkage analysis which influence included sample 513 relative pairs. Increases LOD (chromosome 1, 2,12,19 21), 9), 7 15) minor 21). Understanding factors associated lead achievable goal modification. findings support hypothesis that AD setting future association studies.