APOE gene variability in a sample of the São Paulo brain bank

Abstract

Alzheimer's disease (AD) is the most common form of dementia in the elderly. About 5% of cases are familial, with Mendelian pattern of inheritance and early onset (<40 years old). However, most cases are sporadic, with late-onset and multifactorial inheritance (LOAD or late onset Alzheimer's disease). Several risk factors have been identified so far. Among these are the common polymorphisms of the APOE gene. This gene encodes Apolipoprotein E, a member of a protein family directly related to metabolism and circulation of lipids and cholesterol in the blood plasma. There are three alleles frequently found in the human population: µ2, µ3 and µ4, with variable distribution depending on the specific population studied. The µ4 allele is considered a risk factor for later development of AD and the µ2 allele is considered a protection factor. As late-onset AD is a complex disease, however, APOE genotype is not a perfect predictor of the onset of the disease, since other genetic and environmental factors contribute to the pathophysiology of the disease. Nevertheless, these polymorphisms are recurrently associated with AD. The objective of this study is to investigate the distribution of the APOE gene alleles in a sample of the University of São Paulo Medical School Brain Bank, which provided a sub-sample of about 1600 individuals. A correlational study will be performed with the APOE variants and the diagnosis of AD in this population. This sample will be compared to a group of 1500 elderly currently living in the same city, of which at least 25% remain healthy (cognitively) after 80 years old. The comparative study of the distribution of APOE alleles in those two groups will allow insights in genotype-phenotype correlation associated with healthy longevity and mortality in a large sample of individuals of the Brazilian population. (AU)