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Cited by 8Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

Open access
He, Karen Y., Khramtsova, Ekaterina A., Cabrera-Socorro, Alfredo, Zhang, Yanfei, Li, Shuwei, Sarver, Brice A. J., Smets, Bart, Li, Qingqin S. +4 more·2023·Molecular Neurodegeneration
DOI 10.1186/s13024-023-00684-7PMC PMC10685495
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Abstract

Importance: A few case studies have reported the APOE Christchurch (APOECh) variant to confer protective effects for Alzheimer's disease (AD) and a higher risk of premature cardiovascular disease (CVD). However, these studies primarily focused on a single individual or siblings from the same family. Objective: We sought to characterize the clinical characteristics of individuals with APOECh variation in 455,306 participants of the UK Biobank (UKB) to determine whether it is associated with AD protection or cardiovascular risk. Design, Setting, and Participants: A total of 37 individuals were identified as heterozygous carriers of APOECh in UKB sequencing data as of March 2022, resulting in allele frequency consistent with gnomAD (4.06x10-5). We limited our study to 36 European carriers and generated a noncarrier cohort matched on age, sex, and ancestry. Case-control analyses were performed to evaluate the frequency of 11 binary traits and differences in distributions of 80 quantitative traits and 10 polygenic risk scores (PRS) for lipid traits, CVD, and neurodegenerative diseases. Main Outcomes and Measures: We compared the frequencies of binary traits (binomial distribution probability) and distributions of quantitative traits and PRS (Kolmogorov-Smirnov test). Results: All 37 carriers are free of AD and only 4 have a parental history of AD. There are 22 out of 37 carriers with >1 cardiovascular (CV) condition in clinical and/or self-reported data, two of whom passed away due to heart disease. However, frequency of CVD, dyslipidemia, and hypertension is not enriched in carriers compared with matched non-carriers. Additionally, apolipoprotein B (apoB) is significantly lower in APOECh carriers before (p=0.004) and after statin adjustment (p=0.04). Comparisons of PRS show that carriers and non-carriers have a similar genetic burden of developing dyslipidemia and CVD, but carriers have lower PRS-based AD risk (p=0.02). Conclusions and Relevance: This study demonstrates that APOECh carriers may have lower levels of apoB and a lower risk of AD. Cohorts with enriched cases are needed to further investigate whether the protective effect is linked to APOE genotypes or other factors.

AI snapshot

Written from the paper’s full text.

TL;DR

In UK Biobank whole-exome and whole-genome sequences, 37 heterozygous APOE Christchurch (APOECh) carriers were identified at an allele frequency of 0.004%; none had developed Alzheimer’s disease or mild cognitive impairment by March 2022. Carriers had significantly lower apolipoprotein B and apoB/apoA1 ratio than noncarriers, but analyses were limited by the variant’s rarity and the absence of homozygotes.

Key findings

  • Among 37 heterozygous APOECh carriers (27 females, 10 males; 36 Europeans, 1 admixed American), carriers were enriched for the APOE ε3/ε3 genotype (p = 0.001); 5 carriers (13.9%) were heterozygous for APOE ε4, 30 (83.3%) were homozygous for APOE ε3, and 1 (2.8%) had an ε2/ε3 genotype.
  • No significant differences were detected between carriers and noncarriers for the 19 binary traits assessed; none of the carriers had developed AD or mild cognitive impairment by the March 2022 data freeze, including 4 individuals with parental history of AD. Carriers also showed decreased Alzheimer’s disease polygenic risk score (p = 0.02), which the authors state cannot be attributed to APOECh because the variant is not included in AD GWAS/PRS calculations.
  • Among blood-based lipid biomarkers, apolipoprotein B (apoB) levels were significantly lower in carriers than noncarriers both unadjusted (p = 0.004) and adjusted for self-reported statin use (p = 0.036); carriers also had a lower median apoB/apoA1 ratio (p = 0.047). No difference was found for cerebral amyloid angiopathy or vascular dementia diagnoses.
  • Mendelian randomization analyses of statin-adjusted apoB on AD risk were inconclusive due to confounding by the APOE region, significant heterogeneity, and horizontal pleiotropy; MR using apoB cis-pQTLs and colocalization analysis did not suggest a shared causal variant for apoB and AD.

Methods

  • Observational characterization of APOECh carriers in the UK Biobank using whole-exome sequencing (N = 454,756) and whole-genome sequencing (N = 141,948).
  • Identified 37 heterozygous APOECh carriers and evaluated 19 binary traits related to neurological disorders, cardiovascular disorders, and medication use, plus 80 quantitative traits including blood and urine biomarkers.
  • Lipid biomarkers were compared using a two-sided Kolmogorov-Smirnov test; non-lipid blood biomarkers and hematological traits were assessed at a nominal p < 0.05 level and then considered against multiple testing. Additional analyses included AD polygenic risk score, statin adjustment, Mendelian randomization, and colocalization.

Limitations

  • Stated: no APOECh homozygotes were identified, so the authors could not validate prior findings in a homozygous individual; carrier sample size was insufficient for UKB brain imaging, metabolomics, and proteomics data, and only baseline quantitative measurements were considered.
  • Stated: statin adjustment used only self-reported statin use at baseline, prescription data covered only 48.8% of the UKB cohort, and statin adjustment may be incomplete because not all individuals report medication use; self-reported confounders may be sub-optimally controlled.
  • Evident from the text: the very small number of carriers limits statistical power for rare binary outcomes and direct detection of ICD-coded events such as major adverse cardiovascular events, and replication in larger cohorts is needed.

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

Integrity signals

Registry

Crossref · 10.1186/s13024-023-00684-7

Cites

15 of 15 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

14 of 19 cited sources checked · 7 supported · 0 flagged · accuracy not yet measured

  • Premisecitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    To date, few studies have reported on the effect of APOECh due to limited number of carriers in the population.

    “To date, few studies have reported on the effect of APOECh due to limited number of carriers in the population [5, 6, 8].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [5] Arboleda-Velasquez JF, Lopera F, O’Hare M, Delgado-Tirado S, Marino C, Chmielewska N, et al. Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat Med. 2019;25(11):1680–3. source

      The paper’s unnumbered main text describes APOE3 Christchurch as rare and reports that the authors found no additional carriers homozygous for both APOE3 Christchurch and PSEN1 E280A. It also studies a potential protective effect, but does not state that few studies have reported on APOE3 Christchurch or establish that carrier scarcity is the reason. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [6] Hernandez I, Gelpi E, Molina-Porcel L, Bernal S, Rodriguez-Santiago B, Dols-Icardo O, et al. Heterozygous APOE Christchurch in familial Alzheimer’s disease without mutations in other Mendelian genes. Neuropathol Appl Neurobiol. 2021;47(4):579–82. source
    • cites [8] Rasmussen KL, Tybjaerg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. APOE and dementia - resequencing and genotyping in 105,597 individuals. Alzheimers Dement. 2020;16(12):1624–37. source

      The Discussion (page unavailable) describes a novel report of the APOE3 Christchurch effect in one woman, supporting that evidence on its effect was limited. It also reports low frequencies for nine rare APOE variants, but does not establish that few Christchurch studies exist because carriers are scarce in the population. (LLM, conf=0.80)

      Experimental — accuracy not yet measured
  • Findingcitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    MR analysis of apoB cis protein quantitative trait loci and AD risk was not significant.

    “MR analysis of apoB cis protein quantitative trait loci [15] and AD risk [14] were not significant.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [15] Ferkingstad E, Sulem P, Atlason BA, Sveinbjornsson G, Magnusson MI, Styrmisdottir EL, et al. Large-scale integration of the plasma proteome with genetics and disease. Nat Genet. 2021;53(12):1712–21. source
    • cites [14] Bellenguez C, Kucukali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet. 2022;54(4):412–36. source
  • Findingown data
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    No homozygotes for APOECh were identified in this study.

    “We did not identify any homozygotes for APOECh”
    Quote in the paperSubstantial claim
  • Findingown data
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    No difference was found between APOECh carriers and noncarriers in cerebral amyloid angiopathy or vascular dementia diagnoses.

    “we also assessed for differences in cerebral amyloid angiopathy or vascular dementia diagnoses among carriers and noncarriers, but found no difference”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Among non-lipid blood biomarkers and hematological traits, a few traits showed differences at a nominal level (p < 0.05) but were not significant after accounting for multiple testing.

    “Among non-lipid blood biomarkers and hematological traits, a few traits showed differences at a nominal level (p < 0.05) but were not significant after accounting for multiple testing of 22 non-lipid blood biomarkers or 31 hematological traits”
    Quote in the paperNot a substantial claim
  • May combine two claims. 12
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Study design and conductcitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Statin adjustment may be incomplete because not all individuals report medication use, and confounders assessed by self-report may be sub-optimally controlled.

    “Statin adjustment may be incomplete because not all individuals report medication use; confounders assessed by self-report may be sub-optimally controlled depending on the outcome of interest [16].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [16] Wu Y, Byrne EM, Zheng Z, Kemper KE, Yengo L, Mallett AJ, et al. Genome-wide association study of medication-use and associated disease in the UK Biobank. Nat Commun. 2019;10(1):1891. source

      The Discussion (page unavailable) says self-reported medication use may limit the accuracy of the data, and the Results report that about 73% of participants had non-blank medication information. These passages support concern about incomplete medication data, but the paper does not assess whether statin adjustment or control of self-reported confounders is inadequate for particular outcomes. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Cerebrospinal fluid apoB levels are correlated with tau pathology in pre-symptomatic individuals and elevated in AD patients.

    “a recent study has demonstrated that cerebrospinal fluid apoB levels are correlated with tau pathology in pre-symptomatic individuals and elevated in AD patients [11]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Picard C, Nilsson N, Labonté A, Auld D, Rosa-Neto P, Alzheimer's Disease Neuroimaging Initiative, Ashton NJ, Zetterberg H, Blennow K, Breitner JCB, Villeneuve S, Poirier J, PREVENT-AD research group. Apolipoprotein B is a novel marker for early tau pathology in Alzheimer's disease. Alzheimers Dement. 2022;18(5):875–87. https://doi.org/10.1002/alz.12442. Epub 2021 Sept 29. source

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

    Premisecitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    The APOE gene is a known genetic risk factor for neurodegeneration and cardiovascular disease.

    “The APOE gene is a known genetic risk factor for neurodegeneration and cardiovascular disease (CVD) [1, 2].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [1] Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988;240(4852):622–30. source
    • cites [2] Yamazaki Y, Zhao N, Caulfield TR, Liu CC, Bu G. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat Rev Neurol. 2019;15(9):501–18. source

      The Introduction identifies APOE ε4 as a genetic risk factor for Alzheimer disease and discusses associations with other neurodegenerative conditions. The Biology of APOE section links APOE4 to pro-atherogenic changes, but the cited passages do not establish the broader claim that APOE is a genetic risk factor for cardiovascular disease. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Elevated apoB was significantly associated with increased risk of early onset AD (EOAD) and EOAD cases were enriched for apoB rare functional variants.

    “which observed that elevated apoB was significantly associated with increased risk of early onset AD (EOAD) and EOAD cases were enriched for apoB rare functional variants”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [12] Wingo TS, Cutler DJ, Wingo AP, Le NA, Rabinovici GD, Miller BL, et al. Association of early-onset Alzheimer disease with elevated low-density lipoprotein cholesterol levels and rare genetic coding variants of APOB. JAMA Neurol. 2019;76(7):809–17. source

  • May combine two claims.

    Study design and conductown data
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    The study was unable to validate the findings reported by Arboleda-Velasquez et al. because no homozygotes were identified.

    “and are unable to validate the findings reported by Arboleda-Velasquez et al. [5]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [5] Arboleda-Velasquez JF, Lopera F, O’Hare M, Delgado-Tirado S, Marino C, Chmielewska N, et al. Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat Med. 2019;25(11):1680–3. source

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

    Premisecitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Several rare and protective APOE variants (R154S Christchurch, V236E Jacksonville, and R251G) have been identified recently.

    “Beyond the known effects of APOE ε2 and APOE ε4, several rare and protective APOE variants (R154S Christchurch (APOECh), V236E Jacksonville, and R251G) have been identified recently [3, 4].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [3] Bu G. APOE targeting strategy in Alzheimer’s disease: lessons learned from protective variants. Mol Neurodegener. 2022;17(1):51. source

      The main text identifies Christchurch, Jacksonville (V236E), and R251G as rare protective APOE variants. It labels the Christchurch mutation R136S, however, rather than the claimed R154S; our copy does not explain the difference in numbering. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [4] Rabinovici GD, Dubal DB. Rare APOE Missense Variants-Can We Overcome APOE epsilon4 and Alzheimer Disease Risk? JAMA Neurol. 2022;79(7):649–51. source

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

    Premisecitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    The protective effect of APOECh was observed for a single homozygous individual.

    “The protective effect of APOECh was observed for a single homozygous individual [5] but has been debated for heterozygous individuals [7].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [5] Arboleda-Velasquez JF, Lopera F, O’Hare M, Delgado-Tirado S, Marino C, Chmielewska N, et al. Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat Med. 2019;25(11):1680–3. source

  • May combine two claims.

    Findingcitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Mendelian randomization analysis assessing the causal effect of statin-adjusted apoB on AD risk was inconclusive due to confounding by the APOE region and significant evidence of heterogeneity and horizontal pleiotropy.

    “mendelian randomization (MR) analysis assessing the causal effect of statin-adjusted apoB [13] on AD risk [14] were inconclusive due to confounding by the APOE region, and significant evidence of heterogeneity and horizontal pleiotropy”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [13] Sinnott-Armstrong N, Tanigawa Y, Amar D, Mars N, Benner C, Aguirre M, et al. Genetics of 35 blood and urine biomarkers in the UK Biobank. Nat Genet. 2021;53(2):185–94. source

      The Results (Genetics of biomarkers) discuss apolipoprotein B, and the Results (Causal inference) describe Mendelian-randomization analyses of biomarkers. But the Online Methods specify statin-related adjustment for LDL, not apoB; the passages do not report an apoB–Alzheimer’s disease analysis or attribute an inconclusive result to APOE confounding, heterogeneity, and horizontal pleiotropy. In the citing sentence, [13] follows 'statin-adjusted apoB,' while [14] follows 'AD risk.' (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [14] Bellenguez C, Kucukali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet. 2022;54(4):412–36. source

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

    Premisecitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Higher levels of plasma apoB are associated with AD or cognitive decline.

    “Higher levels of plasma apoB are associated with AD or cognitive decline [9, 10]”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [9] Song F, Poljak A, Crawford J, Kochan NA, Wen W, Cameron B, et al. Plasma apolipoprotein levels are associated with cognitive status and decline in a community cohort of older individuals. PLoS ONE. 2012;7(6):e34078. source

      The Discussion section (‘ApoA1, ApoB and Cognitive Decline’; page unavailable) reports that ApoB is increased in AD plasma, supporting the AD part of the claim. The paper’s own Results (‘Apolipoprotein Levels to Predict Future Cognitive Decline’; page unavailable) do not show a significant association between ApoB alone and subsequent cognitive decline; they show one for the ApoB/ApoA1 ratio. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [10] Xu C, Garcia D, Lu Y, Ozuna K, Adjeroh DA, Wang K, On Behalf Of The Alzheimer's Disease Neuroimaging Initiative. Levels of Angiotensin-Converting Enzyme and Apolipoproteins Are Associated with Alzheimer's Disease and Cardiovascular Diseases. Cells. 2021;11(1):29. https://doi.org/10.3390/cells11010029. source

  • May combine two claims.

    Findingown data
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Among APOECh carriers, 30 (83.3%) are homozygous for APOE ε3, 5 (13.9%) are heterozygous for APOE ε4, and 1 (2.8%) has an ε2/ε3 genotype.

    “five carriers (13.9%) are heterozygous for APOE ε4, 30 (83.3%) are homozygous for APOE ε3, and one (2.8%) has an ε2/ε3 genotype”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Statin adjustment slightly attenuated the difference in apoB levels, but the significant difference persisted.

    “While statin adjustment slightly attenuated the difference in apoB levels, the significant difference persisted”
    Quote in the paperSubstantial claim

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

    Findingown data
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Only one APOECh carrier had one copy of the protective APOE ε2 allele.

    “While only one carrier had one copy of the protective APOE ε2 allele”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Among heterozygous APOECh carriers, none developed AD or mild cognitive impairment by March 2022, including 4 individuals with parental history of AD.

    “Among the heterozygous carriers (age: 56.62–82.06, median: 68.63), none have developed AD or mild cognitive impairment by March 2022 (data freeze used), including 4 individuals with parental history of AD”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    For the quantitative traits assessed, only baseline measurements were considered because repeated biomarker measurements are available only for a subset of UKB participants.

    “For the quantitative traits assessed, only baseline measurements were considered given that repeated biomarker measurements are available only for a subset of UKB participants.”
    Quote in the paperNot a substantial claim

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

    Premisecitation
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    The protective effect of APOECh has been debated for heterozygous individuals.

    “The protective effect of APOECh was observed for a single homozygous individual [5] but has been debated for heterozygous individuals [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Does One Copy of the Christchurch ApoE Variant Slow Alzheimer’s? Alzheimer’s Association International Conference; 2023; Amsterdam, Netherlands.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Study design and conductown data
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Primary care prescription data were not considered for statin adjustment because only 48.8% of the UKB cohort has prescription data.

    “Primary care prescription data were not considered for statin adjustment because only 48.8% of the UKB cohort has prescription data”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Lower apoB and lower apoB/apoA1 ratio together suggest protection from major adverse cardiovascular event (MACE) in APOECh carriers, despite small sample size to directly detect this for ICD-coded events.

    “which together with lower apoB suggests protection from major adverse cardiovascular event (MACE) despite small sample size to directly detect this for ICD-coded events”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Statin adjustment for lipid biomarkers was only applied using self-reported statin use at baseline.

    “Statin adjustment for lipid biomarkers were only applied using self-reported statin at baseline.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data
    § Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants

    Lower apoB may be a characteristic of APOECh carriers and may be protective against AD.

    “suggesting that lower apoB may be a characteristic of APOECh carriers and having lower apoB may be protective against AD”
    Quote in the paperSubstantial claim
19 of 19

  • The paper relies on this without support.

    APOECh is not included in AD genome-wide association studies and PRS calculations.

    “as this rare variant is not included in AD genome-wide association studies and PRS calculations”
1 of 1

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?

  • APOE R136S is a very rare mutation (0.0004% allele frequency in the European population) that was originally described in APOEε2 alleles of people with type III hyperlipoproteinaemia, but is much more common in APOEε3 homozygotes than in any other genotype and has also been associated with increased plasma apolipoprotein B levels.

    “APOE R136S is a very rare mutation (0.0004% allele frequency in the European population37) that was originally described in APOEε2 alleles of people with type III hyperlipoproteinaemia38,39, but is much more common in APOEε3 homozygotes than in any other genotype and has also been associated with increased plasma apolipoprotein B (APOB) levels37.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [37]

    Split into 2 atoms — 0 confirmed, 0 partially supported, 2 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • ApoE2 and the Christchurch variant are associated with lower LDL or ApoB levels.

    “with ApoE2 and Christchurch variant associated with lower LDL51 or ApoB levels52”

    From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [52]

  • The findings potentially explain reported APOE genotype effects on human plasma LDL levels.

    “Our findings thus potentially explain the reported APOE genotype effects on human plasma LDL levels”

    From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [52]

    The lipid-biomarker results (Table 1; page not specified) compare LDL levels in APOE Christchurch carriers and noncarriers, but the reported differences are not statistically significant. The discussion concerns lower apoB levels and calls for further mechanistic work; it does not say that these findings explain reported APOE genotype effects on human plasma LDL levels. I searched for that proposed explanation and for discussion of genotype-related LDL mechanisms. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Does One Copy of the Christchurch ApoE Variant Slow Alzheimer’s? Alzheimer’s Association International Conference; 2023; Amsterdam, Netherlands.

Cited by

Sorted by citations

Related

Authors
He, K. Y., Khramtsova, E. A., Cabrera-Socorro, A., Zhang, Y., Li, S., Sarver, B. A. J., Smets, B., Li, Q. S., De Muynck, L., Parrado, A. R., Lovestone, S., & Black, M. H.
Affiliations
  • Janssen Research & Development (United States) (US)
  • Janssen (Belgium) (BE)
Corresponding author
  • He, Karen Y.
  • Khramtsova, Ekaterina A.
ORCID
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2023-11-28
Volume
18
Issue
1
Pages
92-92
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/s13024-023-00684-7
PMC
PMC10685495
OpenAlex
W4389080501
Semantic Scholar
9ff115cce82f7c56741ae4818046c3ae6adc430c
Cited by
8
References
15
Citations by year
2026: 1 · 2025: 3 · 2024: 4
FWCI
1.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Amgen
  • AstraZeneca
  • GlaxoSmithKline
  • Wellcome Trust
  • UK Research and Innovation
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
apolipoprotein E, APOE ε4 carriers, Alzheimer's disease risk, genetic risk factors, UK Biobank, population genetics
MeSH terms
Alzheimer Disease, Apolipoproteins E, Genotype, United Kingdom, Humans, Biological Specimen Banks, Apolipoprotein E4

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