APOLIPOPROTEIN-E IN THE GENETICS AND EPIDEMIOLOGY OF ALZHEIMERS-DISEASE

The role of apolipoprotein E (ApoE) alleles and isoforms in the etiology and pathogenesis of Alzheimer's disease is discussed. The possibility that ApoE itself is not involved in the disease pathogenesis but is merely in genetic disequilibrium with the real locus is discussed and dismissed. The data showing that the epsilon 4 allele is associated with an increased risk of developing the disease and with an earlier onset age are reviewed. The data showing that, at least in some circumstances, the epsilon 2 allele is associated with a decrease in the risk of developing the disease, and with a later onset age are also reviewed. Data from the genetic analysis of other disorders are reviewed and presented, and it is suggested that the genetic data support the notion that the role of ApoE in the etiology of the disease directly relates to beta-amyloid deposition and plaque formation. This suggestion is in concordance with the most likely mechanism for the role of beta-amyloid precursor protein gene mutations as other risk factors for the disease. (C) 1995 Wiley-Liss, Inc.