Having the ApoE 3/4 or ApoE 4/4 genotype confers a higher risk of developing Alzheimer's disease than the average person.
"Keith and I both found out recently that we are both ApoE 3/4, and this is a gene snip for early onset Alzheimer's. And so you can either be ApoE 3/4 or 4/4, and both of these have a slightly higher risk of getting Alzheimer's than the average person." (said at 0:00:15)
The host claimed that having an ApoE 3/4 or ApoE 4/4 genotype confers a higher risk of developing Alzheimer's disease compared to the average person. Large meta-analyses confirm that carrying one or two copies of the APOE ε4 allele significantly increases the risk of Alzheimer's disease across multiple populations. In a landmark meta-analysis (Farrer et al., JAMA 1997, PMID 9343467) as well as subsequent updated multi-ancestry meta-analyses (Belloy et al., JAMA Neurol 2023, PMID 37930705), the APOE ε3/ε4 genotype confers roughly a 2- to 4.5-fold increased odds of Alzheimer's disease depending on ancestry (e.g., OR = 3.2 to 3.5 in White/Caucasian populations), while the APOE ε4/ε4 genotype increases risk roughly 8- to 15-fold (OR = 14.9 in White populations). Note that while the host described this as a 'gene snip for early onset Alzheimer's', APOE ε4 is actually the primary genetic risk factor for late-onset Alzheimer's disease rather than deterministic early-onset AD caused by APP/PSEN mutations; however, the core assertion that ApoE 3/4 and ApoE 4/4 confer a higher risk than average is well-supported by robust meta-analytic evidence.
- supports: APOE Genotype and Alzheimer Disease Risk Across Age, Sex, and Population Ancestry. (JAMA neurology 2023)
"Odds ratios for APOE*34 and AD risk attenuated following East Asian (OR, 4.54; 95% CI, 3.99-5.17),White (OR, 3.46; 95% CI, 3.27-3.65), Black (OR, 2.18; 95% CI, 1.90-2.49) and Hispanic (OR, 1.90; 95% CI, 1.65-2.18) individuals." (abstract, results, passage verified)
pubmedfull study (doi) - supports: Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype an… (JAMA )
"Among Caucasian subjects from clinic- or autopsy-based studies, the risk of AD was significantly increased for people with genotypes epsilon2/epsilon4 (OR=2.6, 95% CI=1.6-4.0), epsilon3/epsilon4 (OR=3.2, 95% CI=2.8-3.8), and epsilon4/epsilon4 (OR=14.9, 95% CI= 10.8-20.6)" (abstract, results, passage verified)
pubmed