Apolipoprotein E-η4 allele and familial risk in Alzheimer's disease

✍ Scribed by Ge Li; Jeremy M. Silverman; Larry D. Altstiel; Vahram Haroutunian; Daniel P. Perl; Dushyant Purohit; Sandra Birstein; Melinda Lantz; Richard C. Mohs; Kenneth L. Davis

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 910 KB
• Volume: 13
• Category: Article
• ISSN: 0741-0395
• DOI: 10.1002/(sici)1098-2272(1996)13:3<285::aid-gepi5>3.0.co;2-5

✦ Synopsis

Recent studies have 'found an association between presence of apolipoprotein E (APOE) €4 allele and Alzheimer's disease (AD). The present study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the €4 allele with the relatives of AD probands not carrying €4 and with relatives of non-demented controls. Our aim was to determine whether the familial aggregation of PPD in relatives of AD probands is primarily due to those carrying €4. Seventy-seven neuropathologically diagnosed AD patients were obtained as probands through our Alzheimer's Disease Research Center Brain Bank. AD probands were genotyped for APOE. As a comparison group, 198 nondemented probands were also included. Through family informants, demographic and diagnostic data were collected on 382 first-degree relatives (age 2 45 years) of AD probands and 848 relatives of the controls. We found that the cumulative risk of PPD in both relatives of AD probands with and without the €4 allele was significantly higher than that in the relatives of non-demented controls. However, the increased risk in the relatives of AD probands with the €4 allele was marginally, but not significantly, lower than the risk in the relatives of probands without €4. A greater likelihood of death by heart diseases over developing PPD in relatives of AD probands with €4 (3.1-fold increase) was found compared to relatives of probands without €4 (1.7-fold increase), especially prior to age 70, although the difference was not statistically significant. The increased familial risk for PPD in the relatives of AD probands with the APOE-€4 allele relative to controls suggests that familial factors in addition to APOE-€4 are risk factors for AD. Differential