Thursday, March 5, 2009

APO-E Gene and Alzheimer's Disease

Apolipoprotein E4 (APOE4) is a genetic risk factor for development of late-onset Alzheimer's disease. Caucasian and Japanese carriers of 2 e4 alleles (i.e., you got a bad gene from both parents) have a 10- to 30-fold increased risk of developing AD by age 75 compared to lucky individuals not carrying any e4 alleles. The gene is encoded on chromosome 19.

More good news: it is associated with a 40-50% increased risk of cardiovascular disease. And fish oil doesn't help - in APOE4s it may raise LDL and lower HDL.

The following is from Medscape authoress Ekaterina Rogaeva, PhD.

APOE Gene on Chromosome 19q13.2

The APOE gene is a genetic locus for inherited susceptibility to late-onset AD (>65 years) that was confirmed in multiple studies. It encodes a lipoprotein involved in cholesterol metabolism and has three common alleles: epsilon 4 (AD-associated), epsilon 3 (neutral), and epsilon 2 (AD-protective). The frequency of the epsilon 2 allele is reduced in AD subjects (~2% versus ~10% in the general population), whereas the frequency of the epsilon 4 allele is significantly increased in individuals with AD (up to 40%). In addition, the epsilon 4 allele is associated with a decreased age at onset: from 90 years for the non-epsilon 4 carriers to ~70 years in patients homozygous for the epsilon 4 allele.

Nevertheless, genetic testing based on the APOE epsilon 4 allele is ambiguous when used as the sole criterion to diagnose AD since not all epsilon 4 carriers will develop disease and epsilon 4 association is not entirely specific to AD. However, in the future, APOE genotypes could be useful in combination with other clinical measures or genetic variations. Indeed, in at least half of AD cases there is no known cause of the disease, suggesting the existence of additional environmental and genetic factors responsible for late-onset AD.

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