ApoE gene and exceptional longevity: Insights from three independent cohorts

Abstract

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. The ApoE gene is associated with the risk of Alzheimer or cardiovascular disease but its influence on exceptional longevity (EL) is uncertain. Our primary purpose was to determine, using a case-control design, if the ApoE gene is associated with EL. We compared ApoE allele/genotype frequencies among the following cohorts: cases (centenarians, most with 1 + major disease condition; n = 163, 100-111 years) and healthy controls (n = 1039, 20-85 years) from Spain; disease-free cases (centenarians; n = 79, 100-104 years) and healthy controls (n = 597, age 27-81 years) from Italy; and cases (centenarians and semi-supercentenarians, most with 1+ major disease condition; n = 729, 100-116 years) and healthy controls (n = 498, 23-59 years) from Japan. Our main findings were twofold. First, the ε4-allele was negatively associated with EL in the three cohorts, with the following odds ratio (OR) values (adjusted by sex) having been found: 0.55 (95% confidence interval (CI): 0.33, 0.94), P = 0.030 (Spain); 0.41 (95%CI: 0.18, 0.99), P = 0.05 (Italy); and 0.35 (95%CI: 0.26, 0.57), P b 0.001 (Japan). Second, although no association was found in the Spanish cohort (OR = 1.42 (95%CI: 0.89, 2.26), P = 0.145), the ε2-allele was positively associated with EL in the Italian (OR = 2.14 (95%CI: 1.18, 3.45), P = 0.01) and Japanese subjects (OR = 1.81 (95%CI: 1.25, 2.63), P = 0.002). Notwithstanding the limitations of case-control designs, our data suggest that the ApoE might be a candidate to influence EL. The ε4-allele appears to decrease the likelihood of reaching EL among individuals of different ethnic/geographic origins. An additional, novel finding of our study was that the ε2-allele might favor EL, at least in the Italian and Japanese cohorts.

Combined Alzheimer's disease and cerebrovascular staging explains advanced dementia cognition

“…We have previously described a similar, low frequency, APOE e4 distribution in an extended population of probable AD cases [48], which is in fact directly related to a lower frequency of APOE e4 within normal Spanish population [49]. Moreover, an additional factor contributing to the low prevalence of the APOE e4 allele could also be related to the comparatively older age of our cohort, as the frequency of APOE e4 allele becomes markedly less frequent with advancing age [49].…”

Genetics and Pharmacology of Longevity

“…Similar findings have been replicated in genome-wide association studies (GWAS) Garatachea et al, 2014). The ε4 variant of APOE has also been consistently associated with late-onset Alzheimer's disease and also with cardiovascular disease (Peila, Rodriguez, & Launer, 2002).…”

“…The ε4 variant of APOE has also been consistently associated with late-onset Alzheimer's disease and also with cardiovascular disease (Peila, Rodriguez, & Launer, 2002). Interestingly the ε2 variant, which has been shown to protect against dementia, has also been associated with extreme longevity, while the ε4 variant of APOE, which is a risk factor for Alzheimer's disease, reduces the likelihood of reaching extreme longevity (Garatachea et al, 2014). APOE encodes for apolipoprotein E, which has important functions in lipid metabolism, immune function, and cognition.…”

Epigenetic considerations of the APOE gene

“…alzgene.org/). Besides AD and CVD, genetic studies have also connected APOE and its ε2/ε3/ε4 alleles to multiple physiological conditions and disorders, including aging (18,19), diabetes (20), dysbetalipoproteinemia (21), frontotemporal dementia (22), fragile X-associated ataxia (23), glomerulopathy (24), Lewy body dementia (25), metabolic syndrome (26), retinal-related disorders (27) disease (28), posttraumatic stress disorder (29), primary progressive aphasia (30), schizophrenia (31), stroke (32), traumatic brain injury (33), and vascular dementia (34).…”