The &lt;EMPH TYPE="ITAL"&gt;APOE&lt;/EMPH&gt;-∊4 Allele and the Risk of Alzheimer Disease Among African Americans, Whites, and Hispanics

Tang, Mingxin; Stern, Yaakov; Marder, Karen; Bell, Karen L.; Gurland, Barry J.; Lantigua, Rafael; Andrews, Howard; Feng, Lei; Tycko, Benjamin; Mayeux, Richard

doi:10.1001/jama.279.10.751

Cited by 679 publications

(532 citation statements)

References 28 publications

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“…There are no other population based studies of dementia incidence in Mexican Americans to which we can compare Publications by [Tang, Stern, et al 1998] [Tang, Cross, et al 2001] refer to Alzheimer's disease not dementia and are concerned with Caribbean Hispanics, not Mexican Hispanics. Mexican ancestry populations differ culturally and genetically from other Spanish speaking populations in the United States.…”

Section: Discussionmentioning

confidence: 99%

“…For African ancestry participants, the OR was 1.84 and not significant. Tang [Tang, Stern, et al 1998] reported no difference in the effect of APOE4 on Alzheimer's for African Americans, Caribbean Hispanics and Caucasians. We could not find any published study that specifically addressed the effect of APOE4 on dementia incidence in people of Mexican ancestry that was done in a populationbased cohort study.…”

Section: Discussionmentioning

confidence: 99%

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C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype

Haan

Aiello

West

et al. 2008

Neurobiology of Aging

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Background-Those with an apolipoprotein APOE4 allele (APOE4) have lower C-reactive protein (CRP) than those without APOE4. Whether APOE4 modifies the effects of CRP on rate of all cause dementia, cognitive impairment or Alzheimer's disease (AD) is not established.Methods-All cause dementia and cognitive impairment without dementia (CIND) was determined over five follow up visits from 1998-2006 in an ongoing cohort of older Latinos. The association between high sensitivity CRP and dementia/CIND, all cause dementia and Alzheimer's disease by APOE4 status was examined in semi-parametric survival models with covariate adjustments.Results-CRP was significantly lower among those with APOE4 than in those without. Among those with APOE4, CRP was associated with lower rates of combined dementia/CIND (HR: 0.60, 95% CL: 0.20-0.91, p=0.03) from a fully adjusted model. Among those with no APOE4, there was no effect of CRP on dementia/CIND rates (HR: 0.94, 95% CL:0.67-1.33).Conclusions-Lower CRP in those with APOE4 may reflect immune effects of the APOE4 genotype. Higher CRP in those with APOE4 may be a marker of better immune function, leading to lower rate of dementia and AD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype

Haan

Aiello

West

et al. 2008

Neurobiology of Aging

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“…The focus on African Americans was warranted not only by the desire to be more inclusive in our clinical research according to NIH guidelines, but also because this group seems to be at increased risk for AD. 13,36 Scholars have argued whether and how to include ethnicity as a focus in genetic research. [37][38][39][40][41][42] Despite this attention, only a few studies provide data about the challenges and impact of expanding ethnic diversity in research about genetic susceptibility testing.…”

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confidence: 99%

Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the REVEAL study experience

Christensen

Roberts

Royal

et al. 2008

Genetics in Medicine

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Purpose: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants. Methods: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicityspecific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease. Results: Review of epidemiological data suggested notable differences in risk between African Americans and whites and that Apolipoprotein E genotype predicts risk in both groups. Discussions about the benefits and risks of stratified risk assessments reached consensus that estimates based on data from whites should not preclude enrolling African Americans, but population-specific risk curves should be created if feasible. Risk models specific to ethnicity, gender, and Apolipoprotein E genotype were subsequently developed for the randomized clinical trial that oversampled African Researchers are identifying a growing number of genetic markers that are associated with increased or decreased risk for common, complex diseases. Consequently, the development of genetic risk assessment and risk communication strategies are areas of critical importance, especially given that laypersons often have a difficult time in understanding probabilistic information. 1,2 Protocols for disclosing genetic information have been developed and refined for various forms of cancer, 3-6 but similar efforts have been made only recently for other diseases. 7,8 One area of recent focus is Alzheimer disease (AD).AD is the most common form of dementia among the elderly, affecting an estimated five million individuals in the United States. Well over 10 million Americans are expected to have the condition by 2050 as the population continues to age. 9 Many risk factors are well-characterized, including age and family history, 10 -14 whereas many others are under investigation, including education level, 15,16 head trauma, 17,18 high blood pressure, 19 caloric intake, and high cholesterol. 20,21 Regarding genetic factors, rare mutations on genes coding for amyloid precursor protein, presenilin 1, and presenilin 2 have been identified that are deterministic for early-onset AD. 22 Apolipoprotein E (APOE), in contrast, affects susceptibility to AD and has three major forms. APOE ⑀3, the most common allele, is found in over half the US population. The ⑀4 allele is associated with increased risk for AD whereas the ⑀2 allele has a protective effect. 23,24 The ⑀4 allele is neither necessary nor sufficient for AD though, and individuals with the ⑀2 allele still have risk for AD. APOE variants are also associated with other conditions such as hyperlipoproteinemia and atherosclerosis 25 and may play a role in the development of ma...

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“…We used a dichotomous classification for participants as either ε4 allele carriers or noncarriers in this analysis; previous research examining the relationship between APOE and cognitive function suggested that the presence of either one or two APOE ε4 alleles could influence the risk of cognitive function in old age (Seeman et al 2005;Tang et al 1998). Among the visit survey participants, we successfully collected sufficient blood samples to analyze the APOE genotype.…”

Section: Study Samplementioning

confidence: 99%

Effects of the APOE ε4 allele and education on cognitive function in Japanese centenarians

Ishioka

Gondo

Fuku

et al. 2016

AGE

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Apolipoprotein E (APOE) ε4 allele and education have been reported to affect the cognitive function in young-old adults. However, the effects and interactions of the ε4 allele and education on cognitive function in very old age, particularly in centenarians, are not well known. We studied 542 Japanese centenarians. Using the data in total of 452 participants (74 men and 378 women, mean age 103.6 ± 3.2 years) who were genotyped and assessed cognitive function with the Mini-Mental States Examination (MMSE), we examined the effects and interactions of the ε4 allele and education on the MMSE score. First, we coded education as three levels: low, middle, and high based on the formal educational levels (analysis 1). Second, to clarify the modifying effect of education, we adopted a new coding for education into two levels, considering a periodical background (around 1900) of gender differences in educational attainments (analysis 2). In analysis 1, the main effects of the ε4 allele and education on the MMSE score were significant after adjusting for age. Further, there was a significant three-way interaction effect between the ε4 allele, education, and gender on the MMSE. Analysis 2 showed that the modifying effect of the ε4 allele by education was observed only in women with the ε4 allele. These findings suggest that both the APOE ε4 allele and education appear to be associated with cognitive function even in centenarians, but the interaction between the ε4 allele and education might depend on gender in this cohort.

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The <EMPH TYPE="ITAL">APOE</EMPH>-∊4 Allele and the Risk of Alzheimer Disease Among African Americans, Whites, and Hispanics

Cited by 679 publications

References 28 publications

C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype

C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype

Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the REVEAL study experience

Effects of the APOE ε4 allele and education on cognitive function in Japanese centenarians

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