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Cited by 22Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

Investigation of the independent role of a rare APOE variant (L28P; APOE*4Pittsburgh) in late-onset Alzheimer disease

Open access
Fan, KangHsien, Francis, Lily, Aslam, M. Muaaz, Bedison, Margret A., Lawrence, Elizabeth, Acharya, Vibha, Snitz, Beth E., Ganguli, Mary +4 more·2023·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2022.11.007PMC PMC9839598
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Abstract

A rare missense APOE variant (L28P; APOE*4Pittsburgh), which is present only in populations with European ancestry, has been reported to be a risk factor for late-onset Alzheimer's disease (LOAD). However, due to the complete linkage disequilibrium of L28P with APOE*4 (C112R), its independent genetic association is uncertain. The original association study implicating L28P with LOAD risk was carried out in a relatively small sample size. In the current study, we have re-evaluated this association in a large case-control sample of 15,762 White U.S. subjects and investigated its independent effect in APOE 3/4 subjects, as L28P has been observed only in the heterozygous state of APOE*4 carriers and 3/4 is the most common genotype containing the APOE*4 allele. The heterozygous carrier frequency of L28P, all with APOE*4, was about 3-fold higher in AD cases than in cognitively intact controls (0.845% vs. 0.277%). The age- and sex-adjusted meta-analysis odds ratio (OR) was 2.87 (95% CI: 1.34 - 6.13; = 0.0066). Among APOE 3/4 subjects, age- and sex-adjusted meta-analysis OR was 1.53 (95% CI: 0.70 - 3.36; p = 0.28), indicating its effect was independent of APOE*4. The lack of statistical significance appears mainly due to the low power of 4138 subjects with the 3/4 genotype (12% power at α= 0.05) compared to the required sample of 139,088 subjects with the 3/4 genotype to detect an OR of 1.5 at α= 0.05 and 80% power. Our data suggesting that L28P has an independent genetic effect on AD risk is reinforced by earlier experimental findings showing that this mutation leads to significant structural and conformational changes in the ApoE4 molecule and can induce functional defects associated with neuronal Aβ42 accumulation and oxidative stress. Additional functional studies in cell-based systems and animal models will help to delineate its functional significance in the etiology of AD.

AI snapshot

Written from the paper’s full text.

TL;DR

In a large White U.S. case-control sample, the rare APOE L28P variant was about 3-fold more frequent in AD cases than controls and associated with AD risk (meta OR 2.87). Among APOE 3/4 subjects, its independent effect was not statistically significant (OR 1.53, p = 0.28), likely due to low power, but the authors suggest it may still act independently of APOE*4.

Key findings

  • Among 15,762 subjects (6,390 AD cases and 9,372 controls), 80 carried L28P, all with APOE*4; L28P carrier frequency was higher in AD cases than controls (0.845% vs 0.277%; P = 1.25E-06), with age- and sex-adjusted meta-analysis OR 2.87 (95% CI: 1.34–6.13; p = 0.0066).
  • In APOE 3/4 subjects, the age- and sex-adjusted meta-analysis OR for L28P was 1.53 (95% CI: 0.70–3.36; p = 0.28); the authors attribute the lack of significance mainly to low power, with 4,138 APOE 3/4 subjects giving 12% power at α = 0.05 and a required 139,088 APOE 3/4 subjects for 80% power to detect OR 1.5.
  • Only TT and TC L28P genotypes were observed; no rare-allele homozygotes (CC) were found.
  • The paper cites prior experimental work that L28P causes structural/conformational changes in ApoE4 and can induce intraneuronal Aβ42 accumulation and oxidative stress, supporting a possible functional effect independent of APOE*4.

Methods

  • Case-control design using 15,762 White U.S. subjects from three major cohorts: Alzheimer’s Disease Sequencing Project (ADSP), Ginkgo Evaluation of Memory (GEM) study, and University of Pittsburgh studies (ADRC, MoVIES, MYHAT).
  • APOE rs429358 and rs7412 genotypes were determined by TaqMan assays in Pittsburgh and GEM samples and derived from whole-exome sequencing in ADSP; L28P was examined across these samples.
  • Logistic regression with age and sex covariates calculated ORs and 95% CIs per study, followed by meta-analysis; analyses were performed in R, and power calculations used G*Power 3.1.

Limitations

  • The paper states that the APOE 3/4 analysis had low power (4,138 subjects; 12% power at α = 0.05) and that much larger samples are needed to confirm the independent association.
  • The paper states that complete linkage disequilibrium of L28P with APOE*4 makes it nearly impossible to fully separate its unique contribution from APOE*4, and that L28P is ultra-rare and observed only in the heterozygous state on APOE*4-containing chromosomes.
  • Evident from the text: the sample is restricted to White U.S. subjects, limiting generalizability; the study is observational/case-control and does not itself provide functional validation, with the authors calling for future cell-based and animal studies.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.neurobiolaging.2022.11.007

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

10 of 24 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    The rare APOE variant L28P is in complete linkage disequilibrium with the APOE*4 allele.

    “due to the complete linkage disequilibrium of L28P with APOE*4 (C112R)”
    • Also stated in: § Introduction · plain
      “This mutation occurs in complete linkage disequilibrium (LD) with the APOE*4 allele, hence named APOE*4Pittsburgh and APOE*4Freiburg”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [9] Farrer, 1997, Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium, JAMA source
    • cites [10] Faul, 2007, G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences, Behav Res Methods source

      The cited paper’s Tests for Proportions section discusses statistical tests, not APOE variants. Searches for L28P, APOE*4, C112R, and linkage disequilibrium found no passage addressing the claimed relationship; the paper does not provide evidence for it. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    Prior association studies of L28P with late-onset Alzheimer's disease used relatively limited samples.

    “The original association study implicating L28P with LOAD risk was carried out in a relatively small sample size.”
    • Also stated in: § Introduction · plain
      “The main drawbacks of aforementioned studies are the use of relatively limited samples”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [9] Farrer, 1997, Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium, JAMA source
    • cites [11] Ganguli, 2010, Prevalence of mild cognitive impairment by multiple classifications: The Monongahela-Youghiogheny Healthy Aging Team (MYHAT) project, Am J Geriatr Psychiatry source

      The Objective and Conclusions discuss classifications and prevalence of mild cognitive impairment, while Results > Sample size and demographics describes the MYHAT cohort. Searches for L28P, late-onset Alzheimer’s disease association studies, and their sample sizes found no passage addressing the attributed claim. Page numbers were not available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [12] Ganguli, 2000, Ten-year incidence of dementia in a rural elderly US community population: the MoVIES Project, Neurology source
    • cites [13] Huang, 2001, Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons, Proc Natl Acad Sci U S A source
    • Rests on an assumption: L28P is an ultra-rare variant and would require a very large sample size.
  • Premisecitation

    In 1999, two groups independently identified a novel and rare missense mutation in the APOE gene (L28P; rs769452) in which leucine is replaced by proline at codon 28.

    “In 1999, two groups independently identified a novel and rare missense mutation in the APOE gene [9, 10] in which the leucine residue is replaced by proline at codon 28 (L28P; rs769452).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [9] Farrer, 1997, Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium, JAMA source
    • cites [10] Faul, 2007, G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences, Behav Res Methods source

      The cited paper’s Tests for Mean Vectors and Tests for Proportions sections discuss statistical power calculations, not APOE mutations. Searches for APOE, L28P, rs769452, and the claimed independent discoveries in 1999 found no passage addressing the claim in our copy; page numbers were unavailable. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
  • Findingown data

    Among APOE 3/4 subjects, the age- and sex-adjusted meta-analysis odds ratio for L28P and Alzheimer's disease was 1.53 (95% CI: 0.70 - 3.36; p= 0.28).

    “Among APOE 3/4 subjects, age- and sex-adjusted meta-analysis OR was 1.53 (95% CI: 0.70 – 3.36; p= 0.28)”
    Quote in the paperSubstantial claim
  • Findingown data

    The L28P carrier frequency was significantly higher in AD cases than controls (0.845% vs 0.277%; P = 1.25E-06).

    “The L28P carrier frequency was significantly higher in AD cases than controls (0.845% vs 0.277%; P = 1.25E-06).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 4
  • May combine two claims. 7

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    APOE*4 is associated with increased risk and earlier age-at-onset of Alzheimer's disease, while APOE*2 is associated with decreased risk and later age-at-onset compared to APOE*3.

    “of which APOE*4 is associated with an increased risk and earlier age-at-onset (AAO) of Alzheimer’s disease (AD), while APOE*2 is associated with decreased risk and later AAO of AD as compared to the wild type APOE*3 [2–6]”
    Quote in the paperNot a substantial claim3 of 5 sources checked
    • cites [2] Argyri, 2014, Molecular basis for increased risk for late-onset Alzheimer disease due to the naturally occurring L28P mutation in apolipoprotein E4, J Biol Chem source

      The passage labeled Abstract (page unavailable) says that carrying APOE*4 increases the risk of late-onset Alzheimer’s disease and lowers its age of onset. It identifies APOE*2 and APOE*3 as isoforms but does not say that APOE*2 decreases risk or delays onset, or explicitly make APOE*3 the comparator for those associations. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [3] Baron, 2003, Apolipoprotein E Pittsburgh variant is not associated with the risk of late-onset Alzheimer's disease in a Spanish population, Am J Med Genet B Neuropsychiatr Genet source
    • cites [4] Beecham, 2017, The Alzheimer's Disease Sequencing Project: Study design and sample selection, Neurol Genet source

      The introduction identifies APOE as a major genetic determinant of late-onset Alzheimer disease, and the ADSP family study design links ε4 to risk considerations and prioritizes ε3/ε4 individuals with earlier onset. Our copy does not state that ε2 lowers risk or delays onset, or make the claimed comparisons with ε3. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [5] Dafnis, 2010, An apolipoprotein E4 fragment can promote intracellular accumulation of amyloid peptide beta 42, J Neurochem source

      The background passage labeled Abstract (page unavailable) says that carrying the ε4 allele increases Alzheimer’s disease risk and lowers the age of onset of late-onset disease. It identifies apoE2 and apoE3 as isoforms but does not say that apoE2 reduces risk or delays onset relative to apoE3; that part of the citing sentence is unsupported by our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [6] DeKosky, 2006, The Ginkgo Evaluation of Memory (GEM) study: design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia, Contemp Clin Trials source

  • Classified as probably not a substantial claim.

    Premisecitation

    L28P has been examined in additional Alzheimer's disease case-control samples since its initial identification.

    “Since then, this variant has been examined in additional AD case-control samples [11–13]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [11] Ganguli, 2010, Prevalence of mild cognitive impairment by multiple classifications: The Monongahela-Youghiogheny Healthy Aging Team (MYHAT) project, Am J Geriatr Psychiatry source

      The Objective and Conclusions describe a population-based study of mild cognitive impairment, not genetic variants or Alzheimer’s disease case-control samples. Searches of our copy for L28P and for additional case-control samples found no passage addressing the claim; section page numbers were unavailable. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [12] Ganguli, 2000, Ten-year incidence of dementia in a rural elderly US community population: the MoVIES Project, Neurology source
    • cites [13] Huang, 2001, Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons, Proc Natl Acad Sci U S A source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ApoE4 fragments have been found in brains of AD patients.

    “ApoE4 fragments have been found in brains of AD patients [27].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Schwarzer, 2007, meta: An R package for meta-analysis, R News source

      The Description and Fleiss1993bin sections (page unavailable) discuss an aspirin meta-analysis example, not ApoE4 or Alzheimer’s disease. Searches for the quoted claim and for apolipoprotein E4 fragments in Alzheimer’s brains found no relevant passage in our copy; the copy is truncated. (LLM, conf=0.72)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    A specific ApoE4 fragment, ApoE4[Δ(166-299)], promotes the cellular uptake of extracellular Aβ42 and results in increased oxidative stress, similar to the effect of L28P.

    “a specific ApoE4 fragment, ApoE4[Δ(166-299)], has previously been found to promote the cellular uptake of extracellular Aβ42 and resulted in increased oxidative stress [28], similar to the effect of L28P.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [28] Yamazaki, 2019, Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies, Nat Rev Neurol source

      The “APOE4 and Aβ pathology > Aβ clearance” section discusses Aβ uptake by cells expressing APOE4, but does not address the ApoE4[Δ(166–299)] fragment or increased oxidative stress. Searches for the fragment, L28P, and oxidative stress found no passage establishing the claimed effect. The reported findings for APOE4-expressing astrocytes cannot establish what this specific fragment does. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    WT ApoE4 is more susceptible to proteolysis than the other ApoE isoforms (E2 and E3).

    “WT ApoE4 is more susceptible to proteolysis than the other ApoE isoforms (E2 and E3)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Schwarzer, 2007, meta: An R package for meta-analysis, R News source

      The copy’s Argument and metabin Details sections discuss meta-analysis methods, not ApoE isoforms or proteolysis. Searches for ApoE4 susceptibility and proteolytic cleavage relative to ApoE2 and ApoE3 found no relevant passage; the copy is truncated. (LLM, conf=0.72)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Among 4,834 AD cases and controls with APOE*4 carriers, 85.62% had the 3/4 genotype, 8.05% had 4/4, and 6.33% had 2/4.

    “Among the 4,834 AD cases and controls with APOE*4 carriers, 85.62% had the 3/4 genotype followed by 4/4 (8.05%) and 2/4 (6.33%) genotypes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Genotyping of L28P revealed two genotypes, TT and TC, and no rare allele homozygosity (CC) was observed.

    “Genotyping of L28P revealed two genotypes, TT and TC; no example of the rare allele homozygosity (CC) was observed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Lipidated L28P significantly reduced the viability of SK-N-SH cells compared to lipidated WT ApoE4, due to greater cellular oxidative stress induced by L28P than WT ApoE4.

    “Furthermore, lipidated L28P significantly reduced the viability of SK-N-SH cells when compared to lipidated WT ApoE4, which was due to greater cellular oxidative stress induced by L28P than WT ApoE4 [26].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Scacchi, 2003, Screening of two mutations at exon 3 of the apolipoprotein E gene (sites 28 and 42) in a sample of patients with sporadic late-onset Alzheimer's disease, Neurobiol Aging source

  • May combine two claims.

    Study design and conductown data

    The 4,138 subjects with the APOE 3/4 genotype had 12% power at α=0.05 to detect an odds ratio of 1.5, whereas 139,088 subjects with the 3/4 genotype would be required for 80% power at α=0.05.

    “low power of 4,138 subjects with the 3/4 genotype (12% power at α= 0.05) compared to the required sample of 139,088 subjects with the 3/4 genotype to detect an OR of 1.5 at α= 0.05 and 80% power”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The L28P mutation is associated with significant structural and conformational changes in wild type ApoE4 that result in intraneuronal Aβ42 accumulation and oxidative stress.

    “This genetic observation is further supported by a comprehensive experimental study in which the L28P mutation was associated with significant structural and conformational changes in the wild type (WT) ApoE4 that resulted in intraneuronal Aβ42 accumulation and oxidative stress [26].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Scacchi, 2003, Screening of two mutations at exon 3 of the apolipoprotein E gene (sites 28 and 42) in a sample of patients with sporadic late-onset Alzheimer's disease, Neurobiol Aging source
10 of 10

  • The paper relies on this without support.

    L28P is present only in populations with European ancestry.

    “which is present only in populations with European ancestry”

  • The paper relies on this without support.

    L28P has been observed only in the heterozygous state of APOE*4 carriers.

    “as L28P has been observed only in the heterozygous state of APOE*4 carriers”
    “as L28P has been observed in the heterozygous state only on the APOE*4–containing chromosome”

  • The paper relies on this without support.

    APOE 3/4 is the most common genotype containing the APOE*4 allele.

    “and 3/4 is the most common genotype containing the APOE*4 allele”
    “and 3/4 is the most common genotype containing the APOE*4 allele”

  • The paper relies on this without support.

    L28P is an ultra-rare variant and would require a very large sample size.

    “considering L28P is an ultra-rare variant and would require a very large sample size”

  • The paper relies on this without support.

    Earlier experimental findings show that L28P leads to significant structural and conformational changes in the ApoE4 molecule and can induce functional defects associated with neuronal Aβ42 accumulation and oxidative stress.

    “reinforced by earlier experimental findings showing that this mutation leads to significant structural and conformational changes in the ApoE4 molecule and can induce functional defects associated with neuronal Aβ42 accumulation and oxidative stress”

  • The paper relies on this without support.

    About 25% of European Whites carry the APOE*4 allele.

    “Considering that about 25% of the European Whites carry the APOE*4 allele”

  • The paper relies on this without support.

    L28P has been observed in the heterozygous state only on the APOE*4-containing chromosome.

    “it has been observed in the heterozygous state only on the APOE*4–containing chromosome”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Studies have reported that APOE4 Freiburg/Pittsburgh (Leu28Pro, Cys112Arg) was structurally unstable and was associated with a higher risk of developing AD than APOE4 (Cys112Arg).

    “Studies have reported that APOE4 Freiburg/Pittsburgh (Leu28Pro, Cys112Arg) was structurally unstable and was associated with a higher risk of developing AD than APOE4 (Cys112Arg)110, 111).”

    From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [111]

    The Introduction identifies L28P as the APOE*4Pittsburgh/Freiburg variant. The Results and Discussion report structural and conformational changes relative to ApoE4, but do not establish that the variant is structurally unstable. They also report a higher estimated AD risk among APOE 3/4 carriers, but the comparison was not statistically significant (OR 1.53, p = 0.28); the paper says the independent risk association needs confirmation. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Cites

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Related

Authors
Fan, K., Francis, L., Aslam, M. M., Bedison, M. A., Lawrence, E., Acharya, V., Snitz, B. E., Ganguli, M., DeKosky, S. T., Lopez, O. L., Feingold, E., & Kamboh, M. I.
Affiliations
  • University of Pittsburgh (US)
  • University of Florida (US)
Corresponding author
Kamboh, M. Ilyas
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2023-02
Volume
122
Pages
107-111
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/j.neurobiolaging.2022.11.007
PMC
PMC9839598
OpenAlex
W4309477414
Semantic Scholar
a8d3740352b9eea61a9c2e14d35d89221c8cd43a
Cited by
21
References
27
Citations by year
2026: 8 · 2025: 7 · 2024: 6
FWCI
2.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Aging (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Health and Human Services (UF1AG047133, U01 AG032984, U54 HG003067, U01AG049505, U24 AG021886, U01AG049507, U01AG049506, AG030653, AG066468, U01AG049508)
  • University of Pennsylvania
  • Broad Institute (U54HG003067)
  • European Commission (QLG2-CT-2002-01254, U01AG016976, 201413, 01254, 014-93-015)
  • ZonMw (050-060-810)
  • Russian Foundation for Basic Research (047.017.043, NWORFBR 047.017.043)
  • Erasmus Medisch Centrum (050-060-810, 014-93-015)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (050.060.810, 014-93-015, NWO-RFBR 047.017.043, 911-03-012, RFBR 047.017.043, 175.010.200, 175.010.2005.011, 047.017.043)
  • National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc085079-024, n01hc085083-027, n01hc085080-026, n01hc085086-022, 5u01hl096899-08, n01hc25195-41-0-1, n01hc55222-0-0-0, 5u01hl096902-08, QLG2-CT-2002-01254, AG030653, AG021886, AG023651, AG064877, AG066468)
  • Uniformed Services University of the Health Sciences (U01AG057659)
  • National Institute on Aging (AG066468, R01AG064877, R01AG023651, U01AG049505, AG023651, AG 07562, R01AG041718, P50AG005133, U01AG016976, AG064877, AG041718, U01AG052409, R01AG020098, R01AG007562, U01AG052410, R01AG030653, R01AG054076, U01AG057659, U01AG032984, R01AG049607, AG033193, R01AG033040, UF1AG047133, U01AG049506, AG032984, R01AG023629, U01AG049507, R56AG064877, U01AG049508, R01AG033193, AG021886, R01AG015928, U01AG052411, U54AG052427, R37AG023651, P30AG066468, U24AG041689, U24AG021886, AG 030653)
  • National Heart, Lung, and Blood Institute (HHSN268201 100012C, HHSN268201100007I, N01 HC085086, HHSN268201100007C, HHSN2682 01100008C, HH-SN-268201100006C, HHSN268201100011C, HHSN2682011-00005I, N01 HC085079, N01 HC085083, HHSN268201500001I, HHSN2682011-­00009I, N01 HC085080, HHSN268201100005C, HHSN 268200800007C, HHSN268201500001C, HHSN268201100005G, HHSN268201100010C, U01HL130114, HHSN268201100011I, U01HL096814, N01-HC-025195, U01-HL-096899, HHSN268201200036C, HHSN26820 1100009C, N01HC085082, U01-HL-096902, R01HL105756, U01HL080295, N01 HC055222, HHSN2682011-00008I, U01HL096917, N01 HC085081, AG033193, R01HL070825, RC2HL102419, U01HL096812)
  • National Institute of Mental Health (T32MH019986)
  • National Human Genome Research Institute (U54HG003067, U54HG003079, HG003273, U54HG003273)
  • National Center for Complementary and Alternative Medicine
  • National Institute of Neurological Disorders and Stroke (R01NS017950)
  • U.S. National Library of Medicine
  • National Center for Complementary and Integrative Health (U01AT000162)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
APOE ε4, late-onset Alzheimer's disease, genetic risk, linkage disequilibrium, European ancestry, amyloid-beta deposition, oxidative stress, statistical power, case-control study, meta-analysis
MeSH terms
Alleles, Alzheimer Disease, Animals, Apolipoproteins E, Genotype, Heterozygote, Apolipoprotein E3, Apolipoprotein E4

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