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Cited by 1Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchLipoproteins and Cardiovascular Health

Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era

Open access
Coraglia, Federico, Cecchetti, Giordano, Rugarli, Giulia, Spinelli, Edoardo G., Ghirelli, Alma, Pisano, Stefano, Canu, Elisa, Filippi, Massimo +1 more·2026·Alzheimer's Research & Therapy
DOI 10.1186/s13195-026-02089-2PMC PMC13403392
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Abstract

Background: Apolipoprotein E (ApoE) ε4 status informs risk stratification and safety management for anti-amyloid therapies, but genotyping typically requires dedicated procedures, longer turnaround times, and higher costs compared with automated laboratory assays. We evaluated an automated plasma approach for ε4 stratification based on proteotyping, the quantification of isoform-specific ApoE proteins to infer ApoE genotype. Methods: We retrospectively included 110 patients (mean age 67.82 ± 10.11 years, 49.1% female) of European ancestry with cognitive impairment across a broad diagnostic spectrum, including 68 AD-spectrum cases, 29 with subjective symptoms, and 16 with other etiologies. ApoE genotyping identified 57 ε4 non-carriers (51.8%), 44 heterozygous carriers (40.0%), and 9 homozygous carriers (8.2%). ApoE4 and total ApoE (PanApoE) were measured on Lumipulse and the ApoE4/PanApoE ratio (ApoE ratio) was derived. Results: The ratio showed excellent separation across genotypes in our cohort. For ε4 carrier identification, both the ratio and ApoE4 achieved an AUC of 1.00 (95% CI 1.00–1.00), whereas PanApoE showed poor discrimination (AUC 0.30, 95% CI 0.20–0.40), reflecting lower PanApoE levels in ε4 carriers. The ratio also accurately distinguished heterozygotes from homozygotes (AUC 1.00, 95% CI 1.00–1.00). Conclusions: Automated plasma ApoE proteotyping mirrored genetic ε4 status. The ApoE ratio provided complete genotype separation, supporting its use for individual-level stratification. These findings should be interpreted cautiously considering the retrospective single-center design and the limited number of ApoE ε4 homozygotes, and require validation in larger, independent cohorts.

AI snapshot

Written from the paper’s full text.

TL;DR

In a retrospective single-center cohort of 110 patients with cognitive impairment, automated plasma ApoE proteotyping using the Lumipulse ApoE4/PanApoE ratio mirrored ApoE genotype and completely separated ε4 non-carriers, heterozygotes, and homozygotes in this sample. The ratio and ApoE4 both achieved AUC 1.00 for ε4 carrier identification, but the authors caution these exploratory findings require validation in larger independent cohorts.

Key findings

  • Among 110 patients (mean age 67.82 ± 10.11 years, 49.1% female), genotyping identified 57 ε4 non-carriers (51.8%), 44 heterozygotes (40.0%), and 9 homozygotes (8.2%). The ApoE ratio showed no overlap across groups: median 0.00% (range 0.00–1.00) in non-carriers, 34.20% (range 8.10–63.00) in heterozygotes, and 185.50% (range 151.50–250.00) in homozygotes.
  • For ε4 carrier identification, both the ApoE ratio and plasma ApoE4 achieved AUC 1.00 (95% CI 1.00–1.00), with no difference between them (ΔAUC 0.00, p = 1.00). PanApoE showed poor discrimination (AUC 0.30, 95% CI 0.20–0.40).
  • PanApoE levels were significantly lower in ε4 carriers than non-carriers (p = 0.002), but did not show an allele-dose pattern and did not distinguish heterozygotes from homozygotes (p = 0.371).
  • Among ε4 carriers, the ratio distinguished heterozygotes from homozygotes with AUC 1.00 (95% CI 1.00–1.00), while ApoE4 had AUC 0.99 (95% CI 0.98–1.00); PanApoE had AUC 0.41.

Methods

  • Retrospective, single-center observational study at a tertiary memory clinic; 110 patients of European ancestry evaluated for cognitive complaints or objective cognitive impairment between November 2023 and September 2025, spanning AD-spectrum (n = 68), subjective symptoms (n = 29), and other etiologies (n = 16).
  • ApoE ε2/ε3/ε4 genotyping by allele-specific real-time PCR targeting rs7412 and rs429358 served as the reference standard; plasma ApoE4 and PanApoE were measured with fully automated chemiluminescent enzyme immunoassays on the Lumipulse G System, and the ApoE4/PanApoE ratio was derived.
  • Group differences were assessed with non-parametric tests (Kruskal–Wallis with pairwise comparisons); ROC analyses with AUCs and 95% CIs evaluated classification of ε4 carrier status and heterozygote-versus-homozygote status, with DeLong tests for pairwise ROC comparisons.

Limitations

  • The paper states that this was a retrospective, single-center study requiring replication in independent cohorts, and that the small number of ε4 homozygotes (n = 9) limits robustness of subgroup analyses, particularly at distribution extremes.
  • The paper states that formal analytical validation and inter-laboratory harmonization are needed before plasma ApoE proteotyping can substitute for genotyping, and that all measurements used the same reagent batch, so inter-batch variability remains untested.
  • The paper notes that rare genetic variants or unexpected biological patterns can cause genotype–proteotype discrepancies and warrant confirmatory strategies; the text also makes evident that no formal sample size or power calculation was performed, no correction for multiple comparisons was applied, and age/sex were not included as covariates.

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

Integrity signals

Registry

Crossref · 10.1186/s13195-026-02089-2

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

38 of 52 cited sources checked · 19 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Previous studies using similar assay approaches have shown that ApoE isoform levels are primarily driven by ApoE genotype, with limited influence of demographic factors.

    “In addition, previous studies using similar assay approaches have shown that ApoE isoform levels are primarily driven by ApoE genotype, with limited influence of demographic factors [27].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [27] Yuri T, Degrieck R, Minczakiewicz D, Sato H, Kamada J, Nakazawa T, Vandenbroucke I, Aoyagi K, Nojima H. Estimation of the allelic status of apolipoprotein E4 isoforms with fully automated LUMIPULSE® assays. Explor Neurosci. 2023;2(5):238–44. source

      The Results report that ApoE4 concentrations generally increased with the number of APOE ε4 alleles, supporting an association between measured levels and genotype. The Discussion says participant biomedical information was limited and calls for comparisons with other racial groups; it does not establish that demographic factors have limited influence or that genotype is the primary driver relative to them. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • Premisecitation

    ApoE genetic testing is often associated with longer turnaround times (from several days to a few months) compared with laboratory assays that can provide results within hours.

    “longer turnaround times (from several days to a few months) compared to laboratory assays that can provide results within hours”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [13] Dubois B, Villain N, Schneider L, Fox N, Campbell N, Galasko D, Kivipelto M, Jessen F, Hanseeuw B, Boada M, et al. Alzheimer Disease as a Clinical-Biological Construct-An International Working Group Recommendation. JAMA Neurol. 2024;81(12):1304–11. source

      The societal-impact section compares protein and genetic biomarkers, and Panel 1 mentions APOE e4, but neither discusses how long testing takes. Searches for turnaround times, APOE genetic testing, and assay result times found no passage supporting the claimed comparison of days to months versus hours; page numbers were not available in our copy. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
    • cites [14] Goldman JS, Hahn SE, Catania JW, LaRusse-Eckert S, Butson MB, Rumbaugh M, Strecker MN, Roberts JS, Burke W, Mayeux R, et al. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011;13(6):597–605. source

      The APOE SUSCEPTIBILITY TESTING section discusses the clinical use and interpretation of APOE genotyping, but gives no turnaround time. A search for turnaround time, several days, months, and hours found no passage comparing APOE testing with faster laboratory assays. Page numbers were unavailable in our copy. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
    • cites [15] Green RC, Roberts JS, Cupples LA, Relkin NR, Whitehouse PJ, Brown T, Eckert SL, Butson M, Sadovnick AD, Quaid KA, et al. Disclosure of APOE genotype for risk of Alzheimer’s disease. N Engl J Med. 2009;361(3):245–54. source

      The Methods > Study Design passage says blood samples were sent for APOE genotyping, but gives no turnaround time. The Methods passages describe follow-up after disclosure, not how long testing took. Searches for turnaround time and the interval between sampling and disclosure found no comparison with laboratory assays that return results within hours. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
  • Premisecitation

    ApoE ε4 status has gained direct clinical relevance in the anti-amyloid era.

    “Importantly, ApoE ε4 status has gained direct clinical relevance in the anti-amyloid era”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [2] Filippi M, Cecchetti G, Spinelli EG, Vezzulli P, Falini A, Agosta F. Amyloid-Related Imaging Abnormalities and beta-Amyloid-Targeting Antibodies: A Systematic Review. JAMA Neurol. 2022;79(3):291–304. source
    • cites [5] van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, et al. Lecanemab in Early Alzheimer’s Disease. N Engl J Med. 2023;388(1):9–21. source
    • cites [8] Sperling R, Salloway S, Brooks DJ, Tampieri D, Barakos J, Fox NC, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, et al. Amyloid-related imaging abnormalities in patients with Alzheimer’s disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol. 2012;11(3):241–9. source
  • Premisecitation

    Both mass-spectrometry-based and immunoassay-based approaches have shown that plasma ApoE isoform quantification can discriminate ε4 carriers from non-carriers with high accuracy.

    “Both mass-spectrometry-based and immunoassay-based approaches have shown that plasma ApoE isoform quantification can discriminate ε4 carriers from non-carriers with high accuracy [16–18].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [16] Baker-Nigh AT, Mawuenyega KG, Bollinger JG, Ovod V, Kasten T, Franklin EE, Liao F, Jiang H, Holtzman D, Cairns NJ, et al. Human Central Nervous System (CNS) ApoE Isoforms Are Increased by Age, Differentially Altered by Amyloidosis, and Relative Amounts Reversed in the CNS Compared with Plasma. J Biol Chem. 2016;291(53):27204–18. source

      The ‘Accuracy of Total and Isoform-specific ApoE Measures’ section (page unavailable) reports plasma measurements by both MS and ELISA, with total ApoE tending to decrease as ε4 copy number increases. But the Discussion says ELISA cannot measure isoforms independently, and Figure 2 reports that the MS measure did not distinguish ε3/ε3 from ε3/ε4 plasma samples. The paper does not establish high-accuracy discrimination of carriers from non-carriers by both approaches. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [17] Martinez-Morillo E, Hansson O, Atagi Y, Bu G, Minthon L, Diamandis EP, Nielsen HM. Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer’s disease patients and controls. Acta Neuropathol. 2014;127(5):633–43. source
    • cites [18] Rasmussen KL. Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review. Atherosclerosis. 2016;255:145–55. source

      The References section (page unavailable) lists a targeted mass-spectrometry assay for plasma ApoE4 and immunoassays for total ApoE concentration. Section 8 (page unavailable) discusses possible isoform-dependent bias in immunoassays. The review does not report that both approaches quantify plasma ApoE isoforms or distinguish ε4 carriers from non-carriers with high accuracy. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
  • Premisecitation

    ApoE genetic testing is often associated with higher costs (typically hundreds of euros) compared with laboratory assays (less than a hundred euros in our setting).

    “is often associated with higher costs (typically in the order of hundreds of euros) and longer turnaround times (from several days to a few months) compared to laboratory assays that can provide results within hours and at substantially lower cost (less than a hundred euros in our setting) [13–15].”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [13] Dubois B, Villain N, Schneider L, Fox N, Campbell N, Galasko D, Kivipelto M, Jessen F, Hanseeuw B, Boada M, et al. Alzheimer Disease as a Clinical-Biological Construct-An International Working Group Recommendation. JAMA Neurol. 2024;81(12):1304–11. source

      The value of biomarkers section discusses validation and reimbursement, and The societal impact compares protein and genetic biomarkers, but neither gives testing prices or turnaround times. Searches for euros, APOE genotyping costs, and turnaround times found no passage supporting the claimed comparison. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [14] Goldman JS, Hahn SE, Catania JW, LaRusse-Eckert S, Butson MB, Rumbaugh M, Strecker MN, Roberts JS, Burke W, Mayeux R, et al. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011;13(6):597–605. source

      The APOE SUSCEPTIBILITY TESTING section discusses clinical use of genotyping and notes that REVEAL participants received testing free of charge, but says that setting was not representative of typical clinical practice. Searches for testing costs and turnaround times found no comparison with laboratory assays or figures in euros. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [15] Green RC, Roberts JS, Cupples LA, Relkin NR, Whitehouse PJ, Brown T, Eckert SL, Butson M, Sadovnick AD, Quaid KA, et al. Disclosure of APOE genotype for risk of Alzheimer’s disease. N Engl J Med. 2009;361(3):245–54. source

      The Methods (Study Design; page unavailable) say that blood samples were sent to Athena Diagnostics for APOE genotyping, but give no price or turnaround time. Searches for costs and turnaround times found no passage comparing genotyping with laboratory assays or supporting the stated euro amounts. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
  • May combine two claims. 39
  • Classified as probably not a substantial claim. 31

  • May combine two claims.

    Findingcitation

    Predefined manufacturer thresholds (<5% for absence of ε4, 5-74% for heterozygosity, ≥75% for homozygosity), pre-specified based on previous studies using the same assay platform, effectively stratified patients in this cohort without cohort-specific optimization, aligning with genotyping results.

    “Importantly, predefined manufacturer thresholds (< 5% for absence of ε4, 5–74% for heterozygosity, ≥ 75% for homozygosity), pre-specified based on previous studies using the same assay platform [27], effectively stratified patients in our cohort without the need for cohort-specific optimization, aligning with genotyping results”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [27] Yuri T, Degrieck R, Minczakiewicz D, Sato H, Kamada J, Nakazawa T, Vandenbroucke I, Aoyagi K, Nojima H. Estimation of the allelic status of apolipoprotein E4 isoforms with fully automated LUMIPULSE® assays. Explor Neurosci. 2023;2(5):238–44. source

      Split into 2 atoms — 0 confirmed, 1 partially supported, 1 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
    • Rests on an assumption: The Lumipulse immunoassay accurately measures plasma ApoE4 and PanApoE concentrations in this cohort.

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

    Premisecitation

    Previous reports indicated reduced plasma ApoE concentrations in ε4 carriers.

    “consistent with previous reports indicating reduced plasma ApoE concentrations in ε4 carriers [17, 18]”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [17] Martinez-Morillo E, Hansson O, Atagi Y, Bu G, Minthon L, Diamandis EP, Nielsen HM. Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer’s disease patients and controls. Acta Neuropathol. 2014;127(5):633–43. source
    • cites [18] Rasmussen KL. Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review. Atherosclerosis. 2016;255:145–55. source

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

    Premisecitation

    The analytical and diagnostic performance of the Lumipulse ApoE4 and PanApoE immunoassays has been previously evaluated in dedicated validation studies.

    “The analytical and diagnostic performance of the Lumipulse ApoE4 and PanApoE immunoassays has been previously evaluated in dedicated validation studies [27].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Yuri T, Degrieck R, Minczakiewicz D, Sato H, Kamada J, Nakazawa T, Vandenbroucke I, Aoyagi K, Nojima H. Estimation of the allelic status of apolipoprotein E4 isoforms with fully automated LUMIPULSE® assays. Explor Neurosci. 2023;2(5):238–44. source

      The Introduction and Results (pages not provided) describe an evaluation of diagnostic concordance between the Lumipulse ApoE4/Pan-ApoE ratio and APOE genotyping in 178 samples. The paper reports assay measurements and ApoE4 specificity, but our copy does not show a dedicated analytical-performance validation of both immunoassays; that part of the claim is unsupported. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Previous studies showed genotype-dependent differences in ApoE concentrations.

    “consistent with previous studies showing genotype-dependent differences in ApoE concentrations [31, 32]”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [31] Rasmussen KL, Tybjaerg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort. Eur Heart J. 2019;40(33):2813–24. source
    • cites [32] Giannisis A, Al-Grety A, Carlsson H, Patra K, Twohig D, Sando SB, Lauridsen C, Berge G, Grontvedt GR, Brathen G, et al. Plasma apolipoprotein E levels in longitudinally followed patients with mild cognitive impairment and Alzheimer’s disease. Alzheimers Res Ther. 2022;14(1):115. source

  • May combine two claims.

    Premisecitation

    The ε4 allele influences disease risk, age at onset, and multiple aspects of the biological phenotype in a dose-dependent manner.

    “influencing disease risk, age at onset, and multiple aspects of the biological phenotype in a dose-dependent manner [6, 7].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [6] Liu CC, Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9(2):106–18. source
    • cites [7] Tiraboschi P, Hansen LA, Masliah E, Alford M, Thal LJ, Corey-Bloom J. Impact of APOE genotype on neuropathologic and neurochemical markers of Alzheimer disease. Neurology. 2004;62(11):1977–83. source

  • May combine two claims.

    Premisecitation

    ApoE genetic testing requires specific consent procedures and may raise ethical and psychological considerations.

    “Genetic testing requires specific consent procedures, may raise ethical and psychological considerations”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [13] Dubois B, Villain N, Schneider L, Fox N, Campbell N, Galasko D, Kivipelto M, Jessen F, Hanseeuw B, Boada M, et al. Alzheimer Disease as a Clinical-Biological Construct-An International Working Group Recommendation. JAMA Neurol. 2024;81(12):1304–11. source

      The societal impact section (page not specified) discusses psychological consequences of an Alzheimer diagnosis in cognitively normal people and says that how amyloid results are disclosed affects patient experience. It does not specify consent procedures for genetic testing or establish that these disclosure concerns apply to ApoE testing in particular. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [14] Goldman JS, Hahn SE, Catania JW, LaRusse-Eckert S, Butson MB, Rumbaugh M, Strecker MN, Roberts JS, Burke W, Mayeux R, et al. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011;13(6):597–605. source
    • cites [15] Green RC, Roberts JS, Cupples LA, Relkin NR, Whitehouse PJ, Brown T, Eckert SL, Butson M, Sadovnick AD, Quaid KA, et al. Disclosure of APOE genotype for risk of Alzheimer’s disease. N Engl J Med. 2009;361(3):245–54. source

      The Methods (Study Design; page not provided) describe telephone and written informed consent and genetic counseling for this APOE study. The Methods (Safety Monitoring) and Discussion address ethical oversight and possible psychological harm. The paper does not establish that these specific consent procedures are required for genetic testing generally. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Study design and conductcitation

    Calibrators and internal quality controls provided by the manufacturer were used according to standard laboratory procedures.

    “Calibrators and internal quality controls provided by the manufacturer were used according to standard laboratory procedures [27, 28].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [27] Yuri T, Degrieck R, Minczakiewicz D, Sato H, Kamada J, Nakazawa T, Vandenbroucke I, Aoyagi K, Nojima H. Estimation of the allelic status of apolipoprotein E4 isoforms with fully automated LUMIPULSE® assays. Explor Neurosci. 2023;2(5):238–44. source

      The ApoE proteotyping section (page unavailable) says samples were tested according to the instructions for use and measurements used a single calibration run. It does not say that manufacturer-provided calibrators or internal quality controls were used. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [28] Lumipulse GII. https://www.fujirebio.com/en/products-solutions/lumipulse-g600ii.

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

  • May combine two claims.

    Premisecitation

    Previous evaluations of Lumipulse-based ApoE proteotyping reported high concordance with ApoE genotyping and accurate discrimination between ε4 non-carriers, heterozygotes, and homozygotes using predefined ratio cut-offs.

    “consistent with previous evaluations of Lumipulse-based ApoE proteotyping reporting high concordance with ApoE genotyping and accurate discrimination between ε4 non-carriers, heterozygotes, and homozygotes using predefined ratio cut-offs [27, 29]”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [27] Yuri T, Degrieck R, Minczakiewicz D, Sato H, Kamada J, Nakazawa T, Vandenbroucke I, Aoyagi K, Nojima H. Estimation of the allelic status of apolipoprotein E4 isoforms with fully automated LUMIPULSE® assays. Explor Neurosci. 2023;2(5):238–44. source
    • cites [29] Degrieck R, Denoyette M, Delanote J, De Jonge M, Umeda K, Yuri T, Umeda DM, Bastard NL, Sato H, Nojima H, et al. Concordance between APOE genotyping and proteotyping using the novel Lumipulse G Pan-ApoE and Lumipulse G ApoE4 RUO assays. Alzheimer’s Dement. 2023;19:24. source

      The Results in the paper’s Abstract report 99.8% concordance with APOE genotyping and say the ApoE4/Pan-ApoE ratio correctly distinguished heterozygous from homozygous ε4 carriers. The copy does not say that predefined ratio cut-offs were used or that the ratio accurately distinguished ε4 non-carriers from carriers. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The Lumipulse G System is increasingly used in clinical and research settings for cerebrospinal fluid and plasma AD biomarker analyses, making it well suited for integrating ApoE proteotyping into routine diagnostic and therapeutic workflows.

    “The Lumipulse G System (Fujirebio), a fully automated chemiluminescent enzyme immunoassay platform, is increasingly used in clinical and research settings for cerebrospinal fluid and plasma AD biomarker analyses, making it well suited for integrating ApoE proteotyping into routine diagnostic and therapeutic workflows [19, 20].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [19] Alcolea D, Pegueroles J, Munoz L, Camacho V, Lopez-Mora D, Fernandez-Leon A, Le Bastard N, Huyck E, Nadal A, Olmedo V, et al. Agreement of amyloid PET and CSF biomarkers for Alzheimer’s disease on Lumipulse. Ann Clin Transl Neurol. 2019;6(9):1815–24. source

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

      Experimental — accuracy not yet measured
    • cites [20] Teunissen CE, Verberk IMW, Thijssen EH, Vermunt L, Hansson O, Zetterberg H, van der Flier WM, Mielke MM, Del Campo M. Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation. Lancet Neurol. 2022;21(1):66–77. source

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationcitation

    In line with previous proposals of a stepwise approach, such a model may balance analytical performance with clinical safety while facilitating timely ε4 stratification in the era of anti-amyloid therapies.

    “In line with previous proposals of a stepwise approach [36, 37], such a model may balance analytical performance with clinical safety while facilitating timely ε4 stratification in the era of anti-amyloid therapies.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [36] Dittrich A, Blennow K, Tan K, Benedet AL, Skoog I, Hoglund K, Ashton NJ, Zetterberg H, Kern S. Evaluation of two plasma-based proteotyping assays against APOE epsilon4 genotyping in a memory clinic setting: The Gothenburg H70 Clinical Studies. Alzheimers Dement. 2025;21(2):e14610. source
    • cites [37] Filippi M, Cecchetti G, Spinelli EG, Ghirelli A, Rugarli G, Pisano S, Canu E, Agosta F. Anti-amyloid therapies and the transformation of Alzheimer’s care pathways: early lessons from the frontline. Lancet Reg Health Eur. 2026;64:101609. source

  • May combine two claims.

    Premisecitation

    Such discrepancies appear infrequent in large series with overall concordance rates exceeding 99%.

    “Although such events appear infrequent in large series with overall concordance rates exceeding 99% [29]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] Degrieck R, Denoyette M, Delanote J, De Jonge M, Umeda K, Yuri T, Umeda DM, Bastard NL, Sato H, Nojima H, et al. Concordance between APOE genotyping and proteotyping using the novel Lumipulse G Pan-ApoE and Lumipulse G ApoE4 RUO assays. Alzheimer’s Dement. 2023;19:24. source

  • May combine two claims.

    Study design and conductcitation

    The relatively small number of ε4 homozygotes in this cohort (n = 9) represents a limitation and may reduce the robustness of subgroup analyses, particularly for genotype stratification.

    “The relatively small number of ε4 homozygotes in our cohort (n = 9), which reflects the relatively low prevalence of this genotype in clinical populations [35], represents a limitation and may reduce the robustness of subgroup analyses, particularly for genotype stratification.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [35] Heffernan AL, Chidgey C, Peng P, Masters CL, Roberts BR. The Neurobiology and Age-Related Prevalence of the epsilon4 Allele of Apolipoprotein E in Alzheimer’s Disease Cohorts. J Mol Neurosci. 2016;60(3):316–24. source

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

    Findingown data

    The distribution of ApoE genotypes was: ε2/ε3 in 4 patients (3.6%), ε2/ε4 in 3 (2.7%), ε3/ε3 in 53 (48.2%), ε3/ε4 in 41 (37.3%), and ε4/ε4 in 9 (8.2%).

    “The distribution of ApoE genotypes was as follows: ε2/ε3 in 4 patients (3.6%), ε2/ε4 in 3 (2.7%), ε3/ε3 in 53 (48.2%), ε3/ε4 in 41 (37.3%), and ε4/ε4 in 9 (8.2%).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Overall, 53 individuals (48.2%) carried at least one ε4 allele.

    “Overall, 53 individuals (48.2%) carried at least one ε4 allele.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Age and sex distribution did not differ significantly across ApoE genotype groups.

    “Age and sex distribution did not differ significantly across ApoE genotype groups (Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    PanApoE levels showed a significant overall group effect (p = 0.002), with lower values observed in ε4 carriers compared with non-carriers.

    “PanApoE levels showed a significant overall group effect (p = 0.002), with lower values observed in ε4 carriers compared with non-carriers (Fig. 1C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    PanApoE distributions largely overlapped across genotype groups and did not exhibit a clear allele-dose pattern.

    “Accordingly, PanApoE distributions largely overlapped across genotype groups and did not exhibit a clear allele-dose pattern.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both plasma ApoE4 concentration and the ApoE ratio demonstrated a clear allele-dose-dependent increase.

    “By contrast, both plasma ApoE4 concentration and the ApoE ratio demonstrated a clear allele-dose–dependent increase.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Although plasma ApoE4 concentration alone also increased markedly with ε4 allele count (p < 0.001), its distributions showed partial overlap between genotype groups, particularly between ε4 non-carriers and heterozygotes, but also between the heterozygous and homozygous groups, and greater inter-individual variability compared with the ratio.

    “Although plasma ApoE4 concentration alone also increased markedly with ε4 allele count (p < 0.001), its distributions showed partial overlap between genotype groups, particularly between ε4 non-carriers and heterozygotes, but also between the heterozygous and homozygous groups, and greater inter-individual variability compared with the ratio (Fig. 1B).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    A total of 110 patients of European ancestry evaluated for cognitive disturbances with available ApoE genotyping were included.

    “A total of 110 patients of European ancestry evaluated for cognitive disturbances with available ApoE genotyping were included in the present analysis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For ε4 carrier identification, both the ratio and ApoE4 achieved an AUC of 1.00 (95% CI 1.00-1.00).

    “For ε4 carrier identification, both the ratio and ApoE4 achieved an AUC of 1.00 (95% CI 1.00–1.00)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Post-hoc comparisons indicated that the PanApoE difference was driven by the contrast between ε4 non-carriers and carriers (p < 0.001), whereas no significant differences were observed between heterozygous and homozygous carriers (p = 0.371).

    “Post-hoc comparisons indicated that this difference was driven by the contrast between ε4 non-carriers (ε2/ε3, ε3/ε3), and carriers (ε2/ε4, ε3/ε4 and ε4/ε4; p < 0.001), whereas no significant differences were observed between heterozygous (ε2/ε4, ε3/ε4) and homozygous (ε4/ε4) carriers (p = 0.371).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The ApoE ratio showed distinct genotype-dependent distributions with a highly significant overall group effect (p < 0.001) and showed separation across genotype groups in this cohort, with no observed overlap between ε4 non-carriers, heterozygotes, and homozygotes.

    “The ApoE ratio showed distinct genotype-dependent distributions with a highly significant overall group effect (p < 0.001) and showed separation across genotype groups in this cohort, with no observed overlap between ε4 non-carriers, heterozygotes, and homozygotes (Fig. 1A).”
    • Also stated in: § Conclusions · plain
      “The ApoE ratio provided complete genotype separation”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    PanApoE did not demonstrate an allele-dose pattern and failed to distinguish between heterozygous and homozygous ε4 carriers, with substantial overlap between groups.

    “However, PanApoE did not demonstrate an allele-dose pattern and failed to distinguish between heterozygous and homozygous ε4 carriers, with substantial overlap between groups.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Lumipulse immunoassay accurately measures plasma ApoE4 and PanApoE concentrations in this cohort.

  • May combine two claims.

    Findingown data

    In this cohort, cases with overlapping ApoE4 concentrations across genotype groups were effectively resolved by the ApoE ratio, supporting its added value for individual-level discrimination.

    “In our cohort, cases with overlapping ApoE4 concentrations across genotype groups were effectively resolved by the ApoE ratio, supporting its added value for individual-level discrimination.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Lumipulse immunoassay accurately measures plasma ApoE4 and PanApoE concentrations in this cohort.

  • May combine two claims.

    Interpretationreasoning

    The lower plasma PanApoE levels in ε4 carriers likely reflect isoform-specific biological properties, including differential turnover rates of ApoE isoforms, with ApoE4 potentially exhibiting faster plasma clearance.

    “These differences likely reflect isoform-specific biological properties, including differential turnover rates of ApoE isoforms, with ApoE4 potentially exhibiting faster plasma clearance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the European regulatory context, ε4 heterozygotes remain eligible for anti-amyloid therapy but require heightened monitoring.

    “while ε4 heterozygotes remain eligible but require heightened monitoring [9, 10].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [9] European Medicines Agency - Kisunla. https://www.ema.europa.eu/en/medicines/human/EPAR/kisunla.

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

    • cites [10] European Medicines Agency - Leqembi. https://www.ema.europa.eu/en/medicines/human/EPAR/leqembi.

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

  • May combine two claims.

    Interpretationreasoning

    The ApoE4/PanApoE ratio may capture underlying biological differences, translating genotype-dependent molecular features into a measurable plasma phenotype.

    “In this context, the ApoE4/PanApoE ratio may capture these underlying biological differences, translating genotype-dependent molecular features into a measurable plasma phenotype.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    Other unmeasured confounders, such as differences in disease status or comorbidities, were not explicitly accounted for in the analysis.

    “However, this does not exclude the potential influence of other unmeasured confounders, such as differences in disease status or comorbidities, which were not explicitly accounted for in the analysis.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The finding of excellent genotype separation for the ApoE ratio should be interpreted cautiously because of the sample size, particularly the limited number of ε4 homozygotes.

    “However, this observation should be interpreted with caution given the sample size, particularly the limited number of ε4 homozygotes, and requires confirmation in larger independent cohorts.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    No missing data were present for the variables included in the analyses.

    “No missing data were present for the variables included in the analyses.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    Potential confounders such as age and sex were not included as covariates, as demographic characteristics were comparable across genotype groups in the study cohort and given the exploratory nature of the analyses.

    “Potential confounders such as age and sex were not included as covariates, as demographic characteristics were comparable across genotype groups in the study cohort and given the exploratory nature of the analyses.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The study was a retrospective, single-center observational study conducted at a tertiary memory clinic.

    “This was a retrospective, single‑center observational study conducted at our tertiary memory clinic”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    No formal correction for multiple comparisons was applied, as the main analyses were pre-specified and focused on a limited number of primary outcomes.

    “No formal correction for multiple comparisons was applied, as the main analyses were pre-specified and focused on a limited number of primary outcomes.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Given the retrospective design, no formal sample size calculation or power analysis was conducted; the sample size was determined by the number of consecutive eligible patients available during the study period.

    “Given the retrospective design, no formal sample size calculation or power analysis was conducted; the sample size was determined by the number of consecutive eligible patients available during the study period.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Study design and conductnone given

    ApoE genotyping was considered the reference standard for ApoE ε4 status.

    “Genotyping was considered the reference standard for ApoE ε4 status.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    PanApoE showed a quantitative shift without genotype discrimination.

    “Three distinct analytical patterns emerged: (1) a quantitative shift without genotype discrimination (PanApoE)”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    All measurements in the present study were performed using the same reagent batch, and additional studies assessing inter-batch variability are required to confirm analytical robustness across different laboratory conditions.

    “Although all measurements in the present study were performed using the same reagent batch, additional studies assessing inter-batch variability are required to confirm analytical robustness across different laboratory conditions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    These findings should be interpreted as preliminary and require validation in larger, independent cohorts.

    “However, these findings should be interpreted as preliminary and require validation in larger, independent cohorts.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The observation of AUC values of 1.00 should be interpreted with caution because these results may reflect cohort-specific characteristics and the relatively limited sample size.

    “However, the observation of AUC values of 1.00 should be interpreted with caution, as these results may reflect cohort-specific characteristics and the relatively limited sample size.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Study design and conductreasoning

    Formal analytical validation and inter-laboratory harmonization studies will be essential before plasma ApoE proteotyping can be considered a substitute for genotyping within structured clinical pathways.

    “Third, formal analytical validation and inter-laboratory harmonization studies will be essential before plasma ApoE proteotyping can be considered a substitute for genotyping within structured clinical pathways.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Study design and conductnone given

    The potential impact of rare genetic variants or unexpected biological patterns warrants cautious interpretation and supports the need for predefined confirmatory strategies.

    “the potential impact of rare genetic variants or unexpected biological patterns warrants cautious interpretation and supports the need for predefined confirmatory strategies.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    This was a retrospective, single-center study conducted in a tertiary memory clinic setting, and replication in independent cohorts is required to confirm generalizability across laboratories and clinical populations.

    “First, this was a retrospective, single-center study conducted in a tertiary memory clinic setting, and replication in independent cohorts is required to confirm generalizability across laboratories and clinical populations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The overlap in ApoE4 distributions did not meaningfully affect carrier versus non-carrier classification at the group level, but becomes clinically relevant when precise discrimination between heterozygous and homozygous ε4 carriers is required.

    “While this overlap did not meaningfully affect carrier versus non-carrier classification at the group level, it becomes clinically relevant when precise discrimination between heterozygous and homozygous ε4 carriers is required.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Even limited overlap in protein distributions may have asymmetric and clinically meaningful consequences: a falsely classified homozygote might be inappropriately excluded from therapy, and a falsely classified heterozygote might be exposed to treatment despite increased ARIA risk.

    “even limited overlap in protein distributions may have asymmetric and clinically meaningful consequences: a falsely classified homozygote (in reality heterozygous) might be inappropriately excluded from therapy and deprived of potential benefit; conversely, a falsely classified heterozygote (homozygous) might be exposed to treatment despite a markedly increased ARIA risk.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationown data

    This approach may provide a rapid and accessible laboratory-based strategy for ApoE ε4 stratification, which may be particularly relevant in the context of emerging anti-amyloid therapies requiring genetic risk assessment.

    “This approach may provide a rapid and accessible laboratory-based strategy for ApoE ε4 stratification, which may be particularly relevant in the context of emerging anti-amyloid therapies requiring genetic risk assessment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    PanApoE reflects a genotype-associated quantitative shift at the population level but lacks the isoform specificity required for individual-level genotype inference.

    “These findings reinforce the notion that PanApoE reflects a genotype-associated quantitative shift at the population level, but lacks the isoform specificity required for individual-level genotype inference.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    The number of ε4 homozygotes was relatively small; larger samples will be necessary to confirm stability of discrimination, particularly at the distribution extremes.

    “Second, the number of ε4 homozygotes was relatively small; although complete genotype separation was observed for the ratio in this dataset, larger samples will be necessary to confirm stability of discrimination, particularly at the distribution extremes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Study design and conductreasoning

    These findings should be considered exploratory and require validation in larger, independent cohorts.

    “These findings should therefore be considered exploratory and require validation in larger, independent cohorts.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Taken together, these findings suggest the potential feasibility of a pragmatic stepwise implementation strategy.

    “Taken together, these findings suggest the potential feasibility a pragmatic stepwise implementation strategy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    ApoE ε4 stratification is not merely prognostic but directly informs treatment eligibility, monitoring intensity, and individualized risk-benefit discussions.

    “Thus, ε4 stratification is not merely prognostic but directly informs treatment eligibility, monitoring intensity, and individualized risk–benefit discussions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    Although further multicenter validation is needed, plasma-based ApoE proteotyping may represent a practical first-line tool to guide patient selection for confirmatory genotyping in clinical practice.

    “Although further multicenter validation is needed, plasma-based ApoE proteotyping may represent a practical first-line tool to guide patient selection for confirmatory genotyping in clinical practice.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The clear separation observed in this cohort with the ApoE ratio assumes particular relevance in this therapeutic context.

    “Against this background, the clear separation observed in this cohort with the ApoE ratio assumes particular relevance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Plasma ApoE proteotyping, particularly through the ApoE ratio, may represent a promising approach as an initial screening or stratification tool in memory clinic settings, allowing rapid and laboratory-based identification of individuals likely to carry the ε4 allele.

    “Plasma ApoE proteotyping, particularly through the ApoE ratio, may represent a promising approach as an initial screening or stratification tool in memory clinic settings, allowing rapid and laboratory-based identification of individuals likely to carry the ε4 allele.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    This approach remains exploratory and requires validation in larger, independent cohorts, and cannot currently replace genotyping as the reference standard.

    “However, this approach remains exploratory and requires validation in larger, independent cohorts, and cannot currently replace genotyping as the reference standard.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Protein-based approaches may help mitigate some ethical and psychological considerations associated with genetic testing, as they rely on biomarker measurements rather than direct genetic disclosure.

    “From a broader perspective, protein-based approaches may also help mitigate some of the ethical and psychological considerations associated with genetic testing, as they rely on biomarker measurements rather than direct genetic disclosure.”
    Quote in the paperNot a substantial claim
56 of 56

  • The paper relies on this without support.

    Data remain limited on the performance of automated plasma ApoE4 and PanApoE assays for reliably reproducing ApoE ε4 carrier status across heterogeneous populations encountered in memory clinic settings.

    “However, data remain limited on the performance of automated plasma ApoE4 and PanApoE assays for reliably reproducing ApoE ε4 carrier status across the heterogeneous populations encountered in memory clinic settings.”

  • The paper relies on this without support.

    The use of a fully automated platform with standardized reagent handling, calibration procedures, and controlled assay conditions ensures robust performance and supports inter-run consistency.

    “The use of a fully automated platform with standardized reagent handling, calibration procedures, and controlled assay conditions ensures robust performance and supports inter-run consistency.”

  • The paper relies on this without support.

    In everyday clinical practice, ApoE information is frequently needed not to establish a genetic diagnosis, but to support timely therapeutic decisions.

    “In everyday clinical practice, ApoE information is frequently needed not to establish a genetic diagnosis, but to support timely therapeutic decisions.”

  • The paper relies on this without support.

    Fully automated immunoassay platforms enable standardized, high-throughput testing within existing clinical laboratory infrastructures.

    “fully automated immunoassay platforms are particularly attractive because they enable standardized, high-throughput testing within existing clinical laboratory infrastructures.”

  • The paper relies on this without support.

    The Lumipulse immunoassay accurately measures plasma ApoE4 and PanApoE concentrations in this cohort.

    “Although all measurements in the present study were performed using the same reagent batch, additional studies assessing inter-batch variability are required to confirm analytical robustness across different laboratory conditions.”
    “Third, formal analytical validation and inter-laboratory harmonization studies will be essential before plasma ApoE proteotyping can be considered a substitute for genotyping within structured clinical pathways.”
5 of 5

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Claimed ApoE4 overlap conflicts with reported ranges

    Minor

    The text says ApoE4 concentrations partially overlapped between non-carriers and heterozygotes, but Table 1 reports a non-carrier maximum of 0.10 μg/mL and a heterozygote minimum of 0.90 μg/mL.

  • Abstract diagnostic groups exceed the cohort size

    Minor

    The three diagnostic groups listed in the abstract total 113 patients, not 110. The Results section instead reports 13 patients with other etiologies, which would bring the total to 110.

    Reported 110 · recomputed 113

  • Figure caption misidentifies the non-carrier genotypes

    Minor

    The figure caption lists ε2/ε2 and ε2/ε3 as the non-carrier genotypes, whereas the Results section says the non-carriers were ε2/ε3 or ε3/ε3 and reports no ε2/ε2 patients.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Association AP. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision, 5th ed., text rev. edn. Washington, DC: American Psychiatric Association Publishing; 2022.

Cited by

Sorted by citations

Related

Authors
Coraglia, F., Cecchetti, G., Rugarli, G., Spinelli, E. G., Ghirelli, A., Pisano, S., Canu, E., Filippi, M., & Agosta, F.
Affiliations
  • Vita-Salute San Raffaele University (IT)
  • IRCCS Ospedale San Raffaele (IT)
Corresponding author
Agosta, Federica
ORCID
Venue
Alzheimer's Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2026-05-21
Volume
18
Issue
1
ISSN
1758-9193 (ISSN-L)
DOI
10.1186/s13195-026-02089-2
PMC
PMC13403392
OpenAlex
W7161950090
Semantic Scholar
7642fb8fdb556745bdd0ef11f9ddf5f8e12bc359
Cited by
1
References
33
Citations by year
2026: 1
FWCI
4.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s Research & Therapy (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
apolipoprotein E, APOE ε4, APOE genotype, anti-amyloid therapy, risk stratification, Alzheimer's disease, cognitive impairment
MeSH terms
Aged, Alzheimer Disease, Apolipoproteins E, Female, Genotype, Heterozygote, Humans, Male, Middle Aged, Retrospective Studies, Apolipoprotein E4, Cognitive Dysfunction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-01.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-01.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

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