APOLIPOPROTEIN E-EPSILON-4 ALLELE AND FAMILIAL RISK IN ALZHEIMERS-DISEASE

Recent studies have found an association between presence of apolipopr otein E (APOE) epsilon 4 allele and Alzheimer's disease (AD). The pres ent study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the e psilon 4 allele with the relatives of AD probands not carrying epsilon 4 and with relatives of non-demented controls. Our aim was to determi ne whether the familial aggregation of PPD in relatives of AD probands is primarily due to those carrying epsilon 4. Seventy-seven neuropath ologically diagnosed AD patients were obtained as probands through our Alzheimer's Disease Research Center Brain Bank. AD probands were geno typed for APOE. As a comparison group, 198 non-demented probands were also included. Through family informants, demographic and diagnostic d ata were collected on 382 first-degree relatives (age greater than or equal to 45 years) of AD probands and 848 relatives of the controls. W e found that the cumulative risk of PPD in both relatives of AD proban ds with and without the epsilon 4 allele was significantly higher than that in the relatives of non-demented controls. However, the increase d risk in the relatives of AD probands with the epsilon 4 allele was m arginally, but not significantly, lower than the risk in the relatives of probands without epsilon 4. A greater likelihood of death by heart diseases over developing PPD in relatives of AD probands with epsilon 4 (3.1-fold increase) was found compared to relatives of probands wit hout epsilon 4 (1.7-fold increase), especially prior to age 70, althou gh the difference was not statistically significant. The increased fam ilial risk for PPD in the relatives of AD probands with the APOE-epsil on 4 allele relative to controls suggests that familial factors in add ition to APOE-epsilon 4 are risk factors for AD. Differential censorsh ip from increased mortality of heart diseases may have prevented a hig her incidence of PPD among the relatives of probands with epsilon 4. ( C) 1996 Wiley-Liss, Inc.