Non-white or non-European descent

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Minorities are underrepresented in health studies, most research on APOE-ε4 and Alzheimer’s has been conducted on white subjects of European descent. Further compounding this situation is that much of the research conducted on health conditions that affect ApoE4s: Alzheimer’s, Cardiovascular disease, shortened longevity, etc. often do not stratify by APOE status much less racial/ethnic status. One would think genes are color blind, and yet there are differences in non-European ApoE4s. So what to believe? This wiki is dedicated to sharing what research is available.

Black

According to this article Researchers Explain Why Black Americans Are At Higher Risk For Alzheimer's (Meghan Rabbitt, 24 Jun 2020) less than 5 percent of participants in U.S. health studies are black yet older African Americans are about twice as likely than non-Hispanic white people to develop Alzheimer’s or other dementias.

So is the key to this statistic that they are black, ApoE4, living in the United States, or some combination of all of these? While the answer is not definitive, in 2005 this paper APOE ε4 is not associated with Alzheimer's disease in elderly Nigerians (Oye Gureje et al, 22 Dec 2005) was published that found Nigerian APOEε4/4 carriers held a very low incidence of Alzheimer’s, contrary to what is generally considered a very high genetic risk. From the abstract of this paper:

Since 1992, research teams from Indiana University and the University of Ibadan have been collecting and comparing data from two diverse, elderly populations to identify risk factors for dementia and Alzheimer's disease. Apolipoprotein E (APOE) was genotyped in 2,245 Nigerian samples. Of these, 830 had a diagnosis: 459 were normal, and 140 had dementia including 123 diagnosed with Alzheimer's disease. In contrast with other populations, the APOE ε4 allele was not significantly associated with Alzheimer's disease or dementia. This lack of association in the Yoruba might reflect genetic variation, environmental factors, as well as genetic/environmental interactions.

From this Key Alzheimer’s gene acts differently in non-Europeans(LA Bline, 15 Nov 2019):

In this study, individuals with African-derived ancestry in their APOE gene had 39 percent lower odds of Alzheimer’s than did individuals with European-derived APOE.

According to the Alzheimer’s Association Alzheimer’s Disease Facts and Figures report, older African Americans are about twice as likely to have Alzheimer’s or other dementias as older whites. So what is driving the higher rate of dementia in African Americans? According to this article, Alzheimer's risk factors may be measurable in adolescents and young adults (Science News, 30 Jul 2020) the risk factors that are disproportionately apparent in African Americans include heart health factors -- such as high blood pressure, high cholesterol and diabetes -- and social factors like education quality. But this is conjecture, as cited above, black Americans are sorely underrepresented in health studies.

Fortunately, there is more all-inclusive research is being conducted. This press release addresses four studies NIH expands nation’s Alzheimer’s and related dementias research capacity (National Institutes of Health, 10 Sep 2020):

To further incentivize innovative ideas and opportunities in Alzheimer's disease and related dementias research, the National Institute on Aging (NIA), part of the National Institutes of Health, has funded four exploratory Alzheimer’s Disease Research Centers (ADRCs). These new centers will broaden current ADRC research initiatives with underrepresented populations such as African Americans, Native Americans, and those in rural communities — all of which have different risk factors for developing these devastating diseases.

Whether these studies will separate APOE genetic status is unknown.


For further exploration:

From Racial Differences in Dietary Relations to Cognitive Decline and Alzheimer’s Disease Risk: Do We Know Enough? (Puja Agarwal et al, 3 Sep 2020):

In the past few decades, diet has been identified as an important modifiable risk factor for cognitive decline and Alzheimer’s disease. Some studies report poor diet quality among African American and Hispanic older adult populations compared to their white counterparts. We have a limited understanding of how diet affects brain health in different racial-ethnic groups. One primary reason for our lack of knowledge is that most cohort studies are of majority non-Hispanic white participants. Moreover, those that do include minority participants do not publish their findings stratified by racial-ethnic groups, and likely have a less accurate measurement of dietary intake among minority groups. In this review, we summarize the current, albeit limited, literature on racial/ethnic differences in dietary relations to dementia outcomes. We will also discuss methodological issues in conducting nutrition studies in diverse cultures, and suggestions for future research directions. Overcoming the gaps will make it possible to make dietary recommendations for Alzheimer’s prevention that are more relevant for different racial/ethnic groups and set us on a faster track to reduce health disparities.” (Bold font added to quote for emphasis).

Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel (Brian W. Kunkle et al, 19 Oct 2020):

Findings: In this genome-wide association meta-analysis of 2748 individuals with Alzheimer disease and 5222 controls, several novel genetic loci and pathways associated with Alzheimer disease in African American individuals were identified.
Meaning: While the major pathways involved in Alzheimer disease etiology in African American individuals are largely similar to those in non-Hispanic White individuals, many of the disease-associated loci within these pathways differ.

Some insight may also be gained by reviewing the below section on the Hispanics as some population have more African ancestry and differences were found in those Hispanics with African ancestry vs European ancestry.


Hispanic, Latino, etc.

Association between ApoE ε4 Carrier Status and Cardiovascular Risk Factors on Mild Cognitive Impairment among Mexican Older Adults (Sara G. Aguilar-Navarro et al, 14 Nov 2020)

Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer’s disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI [Mild Cognitive Impairment] subtypes (amnestic and non-amnestic) in Mexican older adults.

APOE alleles’ association with cognitive function differs across Hispanic/Latino groups and genetic ancestry in the study of Latinos‐investigation of neurocognitive aging (HCHS/SOL) (Einat Granot‐Hershkovitz et al, 6 Nov 2020) This research took on six Latino subgroups as they differ based on what proportion of their genes trace back to African, European, and Amerindian (indigenous American) ancestries. Cuban individuals have the lowest proportion of Amerindian ancestry of the six groups and a relatively higher proportion of European ancestry.

Results: APOE ε4 was associated with an increased risk of significant cognitive decline (odds ratio [OR] = 1.15, P‐value = 0.03), with the strongest association in Cubans (OR = 1.46, P‐value = 0.007). APOE‐ε2 was associated with decreased risk of MCI (OR = 0.37, P‐value = 0.04) in Puerto Ricans. Amerindian genetic ancestry was found to protect from the risk conferred by APOE ε4 on significant cognitive decline.
Discussion: Results suggest that APOE alleles' effects on cognitive outcomes differ across six Latino backgrounds and are modified by continental genetic ancestry.

Local ancestry at APOE modifies Alzheimer's disease risk in Caribbean Hispanics (Elizabeth E. Blue, et al. 9 Oct 2019) The study looked at the relationship between APOE and Alzheimer's between 3,067 Caribbean Hispanics and 3,028 individuals of European descent. They found that individuals with African-derived ancestry in their APOE gene had 39 percent lower odds of Alzheimer's than individuals with European-derived APOE.

Results: Among the Caribbean Hispanics, individuals with African‐derived ancestry at APOE had 39% lower odds of AD than individuals with European‐derived APOE, after adjusting for APOE genotype, age, and genome‐wide ancestry. While APOE E2 and E4 effects on AD risk and age at onset were significant in the Caribbean Hispanics, they were substantially attenuated compared with those in European ancestry individuals.
Discussion: These results suggest that additional genetic variation in the APOE region influences AD risk beyond APOE E2/E3/E4.

Genetics of cognitive trajectory in Brazilians: 15 years of follow-up from the Bambuí-Epigen Cohort Study of Aging (Mateus H. Gouveia et al, 2 Dec 2019) Latin American populations have some of the highest prevalence rates of dementia in the world, but are under-studied. Recognizing that most genetic risk factors for Age-related Cognitive Decline (ACD) come from European populations, this research focused on Latin American population, examining genetic factors of 1,407 older Brazilians over 15 years.

Abstract: Age-related cognitive decline (ACD) is the gradual process of decreasing of cognitive function over age. Most genetic risk factors for ACD have been identified in European populations and there are no reports in admixed Latin American individuals. We performed admixture mapping, genome-wide association analysis (GWAS), and fine-mapping to examine genetic factors associated with 15-year cognitive trajectory in 1,407 Brazilian older adults, comprising 14,956 Mini-Mental State Examination measures. Participants were enrolled as part of the Bambuí-Epigen Cohort Study of Aging. Our admixture mapping analysis identified a genomic region (3p24.2) in which increased Native American ancestry was significantly associated with faster ACD. Fine-mapping of this region identified a single nucleotide polymorphism (SNP) rs142380904 (β = −0.044, SE = 0.01, p = 7.5 × 10−5) associated with ACD. In addition, our GWAS identified 24 associated SNPs, most in genes previously reported to influence cognitive function. The top six associated SNPs accounted for 18.5% of the ACD variance in our data. Furthermore, our longitudinal study replicated previous GWAS hits for cognitive decline and Alzheimer’s disease. Our 15-year longitudinal study identified both ancestry-specific and cosmopolitan genetic variants associated with ACD in Brazilians, highlighting the need for more trans-ancestry genomic studies, especially in underrepresented ethnic groups.


Native American

Given that some Hispanic populations hold a considerable percentage of Native American ancestry, review of the above discussion may be of interest.

(Research on APOEε4 allele among Native Americans needs to go here.)

This press release addresses four studies NIH expands nation’s Alzheimer’s and related dementias research capacity (National Institutes of Health, 10 Sep 2020):

To further incentivize innovative ideas and opportunities in Alzheimer's disease and related dementias research, the National Institute on Aging (NIA), part of the National Institutes of Health, has funded four exploratory Alzheimer’s Disease Research Centers (ADRCs). These new centers will broaden current ADRC research initiatives with underrepresented populations such as African Americans, Native Americans, and those in rural communities — all of which have different risk factors for developing these devastating diseases.

Whether these studies will separate APOE genetic status is unknown


Asian

APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline (Steve R Makkar et al, Oct 2020) Participants included 19,225 individuals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years.

APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

APOE gene polymorphism in long-lived individuals from a central China population (Guodong Liu et al, 12 Jun 2017) Holding the ApoEε4 allele is typically negatively correlated with longevity, however this paper has found that carriage of ε4 in central China is associated with longevity. In southern and eastern China, this correlation does not hold up.