An investigation into risk factors of Alzheimer's disease : association with pre-clinical, clinical and autopsy confirmed AD

[Truncated] Alzheimer's disease (AD) is the most commonly diagnosed form of dementia in the elderly. Predominantly this disease is sporadic in nature with only a small percentage of cases exhibiting a familial trait. Whilst early-onset AD may be explained by single gene defects, most AD cases are late-onset (>65 years), and although there is no known definite cause for this form of the disease, there are several known risk factors. Of these, the ε4 allele of the apolipoprotein E gene (APOE) is a major risk factor. Unlike the pathogenic mutations in the amyloid precursor or those in the presenilins, APOE ε4 alleles increase risk for AD but are not causative, even when both copies are present. In addition to the polymorphism at the ε2/ε3/ε4 locus, which determines what type of apoE protein one inherits, polymorphisms within the proximal promoter of the APOE gene have also been identified, which are thought to alter transcription of the APOE gene. Recently a mutation in PSl, namely Glu318Gly, has also been identified as a genetic risk factor for AD.