ApoE2 is Positively Associated with Exceptional Longevity and Decreased Risk of Age-Related Diseases
Exceptional longevity is known to run in families and is due to a combination of factors including maintaining a healthy lifestyle in addition to genetic factors. Studies often define healthy aging as reaching an advanced age, often > 85 years old, free of chronic disease. Findings from recent studies implicate several biological pathways that may contribute to the aging process (1).
Identified from gene association studies, ApoE2 is strongest determinant of longevity and decreased susceptibility to age-related diseases. In studies comparing genotype frequencies of centenarians to disease-free younger controls found that the E4 allele reduced the odds of achieving longevity by 45-65% and the E2 allele was associated with an increased likelihood of longevity (2).
in addition, the E4 allele is associated with increased risk of Alzheimer's disease whereas the E2 allele is known to be protective. Two recent studies relating the appearance of amyloid in the brain by PET scans to the onset of dementia show that the ApoE4 carriers had increased occurrence of amyloid. Notably, the ten E2/ E2 subjects in this study were devoid of any identifiable amyloid and would have a reduced risk of presenting with Aβ-mediated diseases (3). Other studies show an association between ApoE4 and age-related cognitive decline, osteoporosis, breast cancer, end-stage renal disease, atherosclerosis and coronary disease (4, 5). The E2 allele is also associated with decreased levels of serum cholesterol and a lower risk of cardiovascular diseases (5).
(1) Shadyab, A. H. et al, Aging Res Rev 2015; 19: 1-7.
(2) Garatachea, N. et al, Exp Gerontol 2014; 53: 16-23.
(3) a) Jansen, W. J. et al, JAMA 2015; 313(19): 1924-1938. b) Ossenkoppele, R. JAMA 2015; 313(19): 1939-1949.
(4) a) Burt, T. D. et al, Proc Natl Acad Sci USA 2008; 105(25): 8718-8723. b) Mahley, R. W. and Rall Jr., S. C. Annu Rev Genomics Hum Genet 2000; 1: 507-537. c) Weisgraber, K. H. et al, Proc Natl Acad Sci USA 1988; 85(24): 9758-9762.
(5) Rosvall, L. et al, Neurobiol Aging 2009; 30(10): 1545-1551.