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Cited by 1Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchPharmacological Receptor Mechanisms and Effects

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index; 17 of the 65 sources its claims cite were checked for support.

Impact of zervimesine on the neuroinflammatory biomarker GFAP and related proteomic molecular correlates in plasma of participants from a phase 2 clinical trial in Alzheimer’s disease

Open access
Di Caro, Valentina, Cho, Eunah, Thiel, Jill, Lizama, Britney N., Koel-Simmelink, Marleen J.A., Pandey, Kiran, Duong, Duc, Seyfried, Nicholas T., Grundman, Michael, Teunissen, Charlotte E., Zetterberg, Henrik, Blennow, Kaj, Caggiano, Anthony O., Hamby, Mary E.·2026·Alzheimer's Research & Therapy
DOI 10.1186/s13195-026-02025-4PMC PMC13182022
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Abstract

Background: Zervimesine (CT1812) is an investigational brain-penetrant small molecule modulator of the sigma-2 receptor (S2R/ TMEM97 ), currently in clinical development for the treatment of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) that selectively prevents and displaces the binding of amyloid beta (Aβ) and α-synuclein oligomers from neuronal synapses. Given the mechanism of action, it was hypothesized that zervimesine might be more effective in patients with lower levels of AD pathology. Indeed, in the SHINE trial, a completed Phase 2, randomized, double-blind, clinical trial conducted in participants with AD, a robust, 95%, slowing of cognitive decline, as assessed via ADAS-Cog11, was observed in a pre-specified subgroup of participants with lesser AD pathology (i.e., low p-tau217 subgroup) compared to a 38% slowing in the overall modified intent-to-treat (mITT)) population. Methods: In SHINE, exploratory plasma biomarkers were assessed using both a targeted and an unbiased, proteomics discovery approach in plasma from participants at baseline and end of study. Treatment effects of zervimesine relative to placebo were assessed in both the mITT population and in a low p-tau217 subgroup, who entered the study with lower (< 1pg/ml) plasma p-tau217 concentrations. Plasma biomarkers Aβ40, Aβ42, GFAP, NfL and BD-tau were assessed using clinically validated targeted assays, along with untargeted TMT-mass spectrometry (MS)-based discovery proteomics followed by bioinformatic, pathway and correlation analyses. Results: Collectively, plasma biomarker findings in the low p-tau217 subgroup were more robust than in the mITT population. Levels of GFAP were significantly decreased and NfL, Aβ42 and Aβ40 levels trended towards a decrease with zervimesine compared to placebo. Proteomics analyses identified candidate pharmacodynamic biomarkers of zervimesine, and gene ontology and pathway analyses pointed to an impact on amyloid biology, trafficking, lipid metabolism, and immune response. Bioinformatics and correlation analyses with GFAP identified biomarkers that may reflect pathway engagement of S2R and/or decreased neuroinflammation. Conclusions: Exploratory plasma biomarker findings align with the degree of clinical benefit in SHINE mITT and low p-tau217 populations, and support future trial enrichment with patients with lower levels of pathology as defined by lower baseline plasma levels of p-tau217. Trial registration: July 20th, 2018 ClinicalTrials.gov Identifier NCT03507790 https://clinicaltrials.gov/study/NCT03507790 .

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In the SHINE Phase 2 trial, exploratory plasma biomarker and proteomic analyses showed that zervimesine treatment effects were more robust in participants with low baseline plasma p-tau217 (<1 pg/ml) than in the overall mITT population. In that low p-tau217 subgroup, plasma GFAP significantly decreased with zervimesine versus placebo, with trends toward decreases in Aβ42, Aβ40, and NfL.

Key findings

  • In the low p-tau217 subgroup, zervimesine significantly decreased plasma GFAP versus placebo (LS mean −28.35; SE 11.687; p = 0.0186), with trends (p ≤ 0.10) toward reductions in Aβ42, Aβ40, and NfL; no treatment effects or trends were observed in the high p-tau217 subgroup (N = 60).
  • In the mITT population, only plasma BD-tau showed a trend toward reduction versus placebo (p = 0.09); no treatment-related changes were observed in GFAP, NfL, Aβ42, or Aβ40, and no change was seen in Aβ42/40 ratio (LS mean 0.0019; SE 0.00148; p = 0.2048).
  • TMT-MS proteomics detected more than 2000 proteins in mITT plasma; 58 proteins were significantly differentially abundant with zervimesine (53 increased, 5 decreased; p ≤ 0.05), while 103 were differentially abundant in the low p-tau217 subgroup (75 increased, 28 decreased; p ≤ 0.05). Pathway analyses implicated amyloid biology, trafficking, lipid metabolism, and immune response.
  • In the low p-tau217 subgroup, 286 TMT-MS proteins correlated with plasma GFAP in zervimesine-treated participants; after removing 3 shared with placebo, 283 “Drug Selective” correlates remained, and 15 of these were also differentially abundant (zervimesine vs placebo, p ≤ 0.10), including GPX3 and CTSG.

Methods

  • SHINE (NCT03507790) was a completed international, multicenter, randomized, double-blind, placebo-controlled 36-week Phase 2 trial in adults aged 50–85 years with mild to moderate AD (MMSE 18–26); participants were randomized 1:1:1 to placebo, 100 mg, or 300 mg zervimesine orally once daily for 6 months. Plasma biomarker analyses included participants with baseline and 6-month plasma (mITT N = 117; low p-tau217 subgroup N = 57; high p-tau217 subgroup N = 60), with p-tau217 subgroups defined by baseline plasma p-tau217 below versus at/above the median of 1.0 pg/ml.
  • Targeted plasma biomarkers Aβ40, Aβ42, GFAP, and NfL were measured with the SIMOA Neuro4-Plex E Kit, and brain-derived tau with a SIMOA-based assay; change from baseline was calculated.
  • Untargeted discovery proteomics used TMT-MS on the first 57 treatment-compliant participants (n = 20 placebo, n = 37 pooled zervimesine) with baseline and 6-month plasma; low p-tau217 subgroup N = 24 (n = 8 placebo, n = 16 zervimesine). Differential abundance was assessed by ANOVA with unadjusted p ≤ 0.05, followed by GO, STRING, MetaCore pathway analyses, and Pearson correlation of protein change from baseline with plasma GFAP change from baseline in the low p-tau217 subgroup.

Limitations

  • The paper states limited sample size, with even smaller subgroups, which may affect differential abundance analysis and lead to false positives or negatives.
  • The paper states that proteomics differential abundance and correlation analyses used unadjusted p-values without controlling for multiple comparisons, increasing type 1 error risk; candidate biomarkers should be viewed with caution until replicated.
  • The paper states that the p-tau217 subgroup analysis was prespecified but not the primary analysis, and that plasma biomarkers may reflect peripheral changes rather than brain-relevant disease processes; replication in larger trials is warranted.

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

Integrity signals

Registry

Crossref · 10.1186/s13195-026-02025-4

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

17 of 65 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Prior exploratory CSF analyses supported an impact of zervimesine on AD pathophysiology including amyloid biology, synaptic function, inflammation and lipoprotein-related biological processes.

    “These exploratory analyses supported an impact of zervimesine on AD pathophysiology [1, 36, 39, 40] including amyloid biology, synaptic function [4–6], inflammation and lipoprotein-related biological processes [5, 6, 41]”
    Quote in the paperNot a substantial claim4 of 4 sources checked
    • cites [1] Izzo NJ, Yuede CM, LaBarbera KM, Limegrover CS, Rehak C, Yurko R, et al. Preclinical and clinical biomarker studies of CT1812: a novel approach to Alzheimer’s disease modification. Alzheimers Dement. 2021;17:1365–82. https://doi.org/10.1002/alz.12302. source
    • cites [36] Colom-Cadena M, Toombs J, Simzer E, Holt K, McGeachan R, Tulloch J, et al. Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer’s disease. Acta Neuropathol. 2024;147:32. https://doi.org/10.1007/s00401-023-02679-6. source

      The Results section (page unavailable) reports that CT1812 altered pathways important for synaptic function in human iPSC-derived neurons, supporting the synaptic-function portion cited to this paper. The paper does not report exploratory CSF analyses, so it cannot substantiate the claim that those analyses showed this effect. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [39] Izzo NJ, Staniszewski A, To L, Fa M, Teich AF, Saeed F, et al. Alzheimer’s therapeutics targeting amyloid beta 1–42 oligomers I: abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits. PLoS One. 2014;9:e111898. https://doi.org/10.1371/journal.pone.0111898. source

      The Results sections on compound screening and anti-Abeta effects describe candidate drugs tested in neuronal cultures and mice, not exploratory CSF analyses of zervimesine. Our copy does not identify zervimesine or report its effects on the biological processes claimed (searched: zervimesine, CT1812, CSF, inflammation, and lipoproteins). (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites [40] Izzo NJ, Xu J, Zeng C, Kirk MJ, Mozzoni K, Silky C, et al. Alzheimer’s therapeutics targeting amyloid beta 1–42 oligomers II: sigma-2/PGRMC1 receptors mediate abeta 42 oligomer binding and synaptotoxicity. PLoS One. 2014;9:e111899. https://doi.org/10.1371/journal.pone.0111899. source

      The Results section on endogenous Aβ oligomers reports that CT01344 displaced oligomers from postmortem AD brain sections, supporting a related effect on amyloid biology. The paper does not report exploratory CSF analyses or identify an effect of zervimesine on the listed biological processes; its experiments cannot establish that broader claim. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Findingown data

    21 correlates with plasma GFAP levels were found to interact with S2R complex components.

    “B Table of the 21 correlates with plasma GFAP levels found to interact with the S2R complex components and their known biological functions relevant to AD or the zervimesine mechanism of action through S2R”
    Quote in the paperNot a substantial claim
  • Findingown data

    Decrease of CSF NfL levels was observed in the SHINE zervimesine-treated participants.

    “Decrease of CSF NfL levels in the SHINE zervimesine-treated participants further underlines the role of zervimesine in slowing neurodegeneration.”
    Quote in the paperSubstantial claim
  • Findingown data

    In participants treated with zervimesine in the low p-tau217 subgroup, a total of 286 TMT-MS-detected plasma proteins were significantly (p ≤ 0.05) correlated with plasma GFAP levels.

    “In participants treated with zervimesine, a total of 286 TMT-MS-detected plasma proteins were found to be significantly (p ≤ 0.05) correlated with plasma GFAP levels”
    Quote in the paperSubstantial claim
  • Findingown data

    In the low p-tau217 subgroup, a statistically significant decrease in GFAP (zervimesine vs. placebo; LS mean −28.35; SE 11.687; p = 0.0186) was observed.

    “In the low p-tau217 subgroup, a statistically significant decrease in the neuroinflammatory marker GFAP (zervimesine vs. placebo; LS mean​ −28.35; SE 11.687; p = 0.0186) was observed”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim. 19
  • It may state two separate claims as one. 28
  • The quote only partly states this claim. 3

  • Probably not a substantial claim.

    Premisecitation

    Reports from the subgroup analysis of phase 3 trial TRAILBLAZER-ALZ2 suggest that donanemab is more effective in participants with less cognitive impairment and lower tau burden.

    “reports of findings from the subgroup analysis of phase 3 trial TRAILBLAZER-ALZ2 suggest that donanemab is more effective in participants with less cognitive impairment and lower tau burden [16, 18].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [16] Vasudeva R, Doty E, Yang F, Evans C, Zimmer J, Lu M, et al. The Importance of Early Recognition and Treatment Initiation for Managing Alzheimer’s disease: Subpopulation Analysis of the TRAILBLAZER-ALZ 2 Randomized Trial (S23.005). Neurology. 2025;104. https://doi.org/10.1212/WNL.0000000000210512. source
    • cites [18] Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J, et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023;330:512–27. https://doi.org/10.1001/jama.2023.13239. source

      The Discussion reports greater benefit in the low/medium-tau group than in the high-tau group and says this supports a hypothesis of greater benefit when treatment starts earlier. But the Subgroup Analyses section says outcomes were generally consistent across baseline-characteristic subgroups; our copy does not establish greater efficacy specifically among participants with less cognitive impairment. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Premisecitation

    p-tau217 is an extensively validated excellent indicator of degree of amyloid as assessed via CSF analysis and amyloid PET, and tau levels as assessed via tau PET.

    “p-tau217 was selected for this substudy as it is an extensively validated to be an excellent indicator of degree of amyloid as assessed via CSF analysis and amyloid PET, and tau levels as assessed via tau PET [9, 13, 14, 32]”
    Quote in the paperSubstantial claim4 of 4 sources checked
    • cites [9] Mattsson-Carlgren N, Collij LE, Stomrud E, Pichet Binette A, Ossenkoppele R, Smith R, et al. Plasma biomarker strategy for selecting patients with Alzheimer disease for antiamyloid immunotherapies. JAMA Neurol. 2024;81:69–78. https://doi.org/10.1001/jamaneurol.2023.4596. source

      The Abstract and Discussion (page numbers unavailable) report that plasma p-tau217 predicts amyloid positivity defined by CSF or PET and identifies patients likely to have high tau-PET burden; the Discussion also cites prior supporting studies. The paper evaluates amyloid status and categories of tau burden, not how accurately p-tau217 indicates the quantitative degree of amyloid or tau levels across their ranges. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [13] Mattsson-Carlgren N, Janelidze S, Bateman RJ, Smith R, Stomrud E, Serrano GE, et al. Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau. EMBO Mol Med. 2021;13:e14022. https://doi.org/10.15252/emmm.202114022. source

      The Results section reports that plasma p-tau217 was significantly associated with both amyloid PET and tau PET measures, supporting those parts of the claim. This paper does not establish its performance against amyloid measured by CSF analysis; the Introduction discusses CSF biomarkers but does not provide that comparison. Its PET findings also vary by disease stage, so “excellent indicator” is broader than the reported associations. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [14] Ashton NJ, Brum WS, Molfetta GD, Benedet AL, Arslan B, Jonaitis E, et al. Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology. JAMA Neurol. 2024;81:255–63. https://doi.org/10.1001/jamaneurol.2023.5319. source

      The Results section, “Accuracy in Discriminating Abnormal Aβ and Tau Pathologies” (page unavailable), reports high accuracy for identifying abnormal amyloid by CSF and amyloid PET and abnormal tau by tau PET across the studied cohorts. It also reports increasing plasma p-tau217 across tau-PET–defined Braak stages. The evidence is strongest for distinguishing abnormal from normal pathology, rather than for the claimed measurement of the degree of amyloid and tau pathology by each method. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [32] Devanarayan V, Charil A, Horie K, Doherty T, Llano DA, Andreozzi E, et al. Plasma pTau217 ratio predicts continuous regional brain tau accumulation in amyloid-positive early Alzheimer’s disease. Alzheimers Dement. 2025;21:e14411. https://doi.org/10.1002/alz.14411. source

      The Background reports that plasma pTau217R reflects brain amyloid and tau pathology and cites prior findings that it predicts continuous amyloid levels. The Abstract Results report that a pTau217R-based model predicts tau levels measured by PET in amyloid-positive early AD. Our copy does not establish the claimed validation against CSF amyloid measurements, and its findings concern the pTau217 ratio rather than p-tau217 generally. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Premisecitation

    Plasma GFAP is a sensitive biomarker for detecting reactive astrogliosis, a hallmark of neuroinflammation, as well as Aβ pathology, even in early stages of AD.

    “plasma GFAP is a sensitive biomarker for detecting reactive astrogliosis, a hallmark of neuroinflammation, as well as Aβ pathology, even in early stages of AD [33].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [33] Benedet AL, Milà-Alomà M, Vrillon A, Ashton NJ, Pascoal TA, Lussier F, et al. Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the Alzheimer disease continuum. JAMA Neurol. 2021;78:1471. https://doi.org/10.1001/jamaneurol.2021.3671. source

      The Introduction calls blood GFAP a reactive-astrogliosis biomarker, and the Results and Discussion support plasma GFAP as an early indicator of Aβ pathology. However, the Results section on neuroinflammation found that plasma GFAP, unlike CSF GFAP, was not associated with the other glial biomarkers tested. The paper therefore does not establish plasma GFAP as a sensitive detector of neuroinflammation generally. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Premisecitation

    The oligomer receptor prion protein, PrPC, binds TMEM97 (S2R) and amyloid precursor protein (APP).

    “the oligomer receptor prion protein, PrPC, not only binds TMEM97 (S2R) [36], it is also known to bind amyloid precursor protein (APP) [37]”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [36] Colom-Cadena M, Toombs J, Simzer E, Holt K, McGeachan R, Tulloch J, et al. Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer’s disease. Acta Neuropathol. 2024;147:32. https://doi.org/10.1007/s00401-023-02679-6. source

      The Results section reports a FRET signal between TMEM97 and PrPC in human postsynapses, supporting close proximity. The Discussion treats a direct interaction as possible, but the FRET finding does not establish that PrPC binds TMEM97. The APP-binding clause has a separate citation [37] and is not assessed against this source. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [37] Miranzadeh Mahabadi H, Taghibiglou C. Cellular prion protein (PrPc): putative interacting partners and consequences of the interaction. Int J Mol Sci. 2020;21:7058. https://doi.org/10.3390/ijms21197058. source

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation

    The level of plasma p-tau217 is correlated with amyloid and tau pathology on PET imaging and has proven useful in identifying study participants for trials assessing the effects of anti-amyloid therapies.

    “The level of plasma p-tau217 is correlated with amyloid and tau pathology on PET imaging and has proven useful in identifying study participants for trials assessing the effects of anti-amyloid therapies [11–13].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [11] Ashton NJ, Brum WS, Di Molfetta G, Benedet AL, Arslan B, Jonaitis E, et al. Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology. JAMA Neurol. 2024;81:255. https://doi.org/10.1001/jamaneurol.2023.5319. source

      The Results sections on abnormal Aβ and tau pathologies and on other plasma biomarkers report that plasma p-tau217 predicts PET-defined amyloid and tau pathology and correlates with both PET measures (page numbers unavailable in our copy). The Discussion describes promising utility for early Alzheimer disease trials, but says further studies of trial-inclusion designs are warranted. It does not establish that p-tau217 has already proven useful for selecting participants in anti-amyloid therapy trials. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [12] Hu Y, Cho M, Sachdev P, Dage J, Hendrix S, Hansson O, et al. Fluid biomarkers in the context of amyloid-targeting disease-modifying treatments in Alzheimer’s disease. Med. 2024;5:1206–26. https://doi.org/10.1016/j.medj.2024.08.004. source
    • cites [13] Mattsson-Carlgren N, Janelidze S, Bateman RJ, Smith R, Stomrud E, Serrano GE, et al. Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau. EMBO Mol Med. 2021;13:e14022. https://doi.org/10.15252/emmm.202114022. source

      The Results section reports associations between plasma P-tau217 and both amyloid and tau PET measures, supporting the first part of the claim. The paper does not report that plasma P-tau217 has proven useful for selecting participants for anti-amyloid therapy trials; its Participants section says amyloid positivity in the studied cohort was determined by PET. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Premisecitation

    Treatment of neurons with zervimesine restores the functional and synaptic deficits incurred by Aβ oligomers, including restoration of membrane trafficking and prevention of synapse loss.

    “Treatment of neurons with zervimesine restores the functional and synaptic deficits incurred by Aβ oligomers, including the restoration of membrane trafficking, and the prevention of synapse loss [1].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Izzo NJ, Yuede CM, LaBarbera KM, Limegrover CS, Rehak C, Yurko R, et al. Preclinical and clinical biomarker studies of CT1812: a novel approach to Alzheimer’s disease modification. Alzheimers Dement. 2021;17:1365–82. https://doi.org/10.1002/alz.12302. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    IGF2R is important for memory, and its dysregulation may contribute to AD pathology; IGF2R levels decrease with the presence of the APOE4 allele, and overexpression of IGF2R is associated with increased Aβ production.

    “IGF2R is important for memory, and its dysregulation may contribute to AD pathology. IGF2R levels decrease with the presence of the APOE4 allele, which is associated with increased risk for AD and overexpression of IGF2R is also associated to increase Aβ production [51, 52].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [51] Alberini CM. IGF2 in memory, neurodevelopmental disorders, and neurodegenerative diseases. Trends Neurosci. 2023. https://doi.org/10.1016/j.tins.2023.03.007. source

      The section on IGF2 expression and memory reports that blocking or deleting hippocampal IGF2R impairs long-term memory. The CNS diseases section links IGF2R to amyloid reduction in an AD mouse model, but does not report lower IGF2R levels with APOE4 or increased Aβ production from IGF2R overexpression; it instead reports that IGF2 overexpression reduced Aβ, apparently via IGF2R. Page numbers are unavailable in our copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [52] Yu XW, Pandey K, Katzman AC, Alberini CM. A role for CIM6P/IGF2 receptor in memory consolidation and enhancement. Elife. 2020;9:1–25. https://doi.org/10.7554/eLife.54781. source

  • The quote only partly states this claim.

    Findingown data

    In zervimesine vs placebo treated participants, nominally significant trends (p ≤ 0.10) in reducing plasma levels of Aβ40, Aβ42, and NfL were observed in patients with mild to moderate AD that have lower than 1 pg/ml p-tau217 levels at baseline using the AlzPath Dx assay.

    “Nominally significant trends (p ≤ 0.10) in reducing plasma levels of Aβ40, Aβ42, and NfL were also observed in zervimesine vs. placebo treated participants”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

    Findingown data

    Scatter plots of GPX3 and CTSG show favorable correlation of CFB log2 abundance levels with plasma CFB GFAP levels across individual zervimesine-treated patients.

    “Scatter plots of two of these proteins – glutathione peroxidase 3 (GPX3) and cathepsin G (CTSG) – are shown, demonstrating examples of a positive and negative correlation of change in abundance with improvement in plasma GFAP levels”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    In mITT, 58 proteins were significantly differentially abundant with zervimesine treatment (p ≤ 0.05, 53 increased, 5 decreased).

    “of which 58 proteins were significantly differentially abundant with zervimesine treatment (Fig. 2A: zervimesine vs. placebo p ≤ 0.05, 53 increased (red), 5 decreased (green)).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Fifteen proteins met both correlation and differential abundance criteria (from 283 drug-selective GFAP correlates and 197 differentially abundant proteins at p ≤ 0.10 in the low p-tau217 subgroup).

    “Fifteen proteins (Fig. 4C, brown overlap) met both correlation and differential abundance criteria.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Findingreasoning

    283 'Drug Selective' protein correlates (r≥|0.50|) were selected for pathway analyses.

    “only the 283 “Drug Selective” protein correlates (r≥|0.50|) (orange semicircle; top correlates shown in Supplemental Table 3), were selected for pathway analyses”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Candidate biomarkers include early endosome antigen 1 (EEA1), identified in mITT and low p-tau217 groups, and progranulin (GRN) identified in the mITT population.

    “These candidate biomarkers include early endosome antigen 1 (EEA1), identified in mITT and low p-tau217 groups, and progranulin (GRN) identified in the mITT population.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    Data provide insights into the mechanism by which zervimesine may ameliorate AD through S2R, perhaps via dampening neuroinflammation in addition to slowing neurodegeneration.

    “Data provide insights into the mechanism by which zervimesine may ameliorate AD through S2R, perhaps via dampening neuroinflammation in addition to slowing neurodegeneration”
    Quote in the paperSubstantial claim
    • Rests on an assumption: GFAP is a neuroinflammatory biomarker.

  • It may state two separate claims as one.

    Premisecitation

    Plasma biomarkers are less invasive, less costly, and more time-efficient measurements than CSF or neuroimaging biomarkers.

    “Plasma biomarkers are less invasive, less costly, and more time-efficient measurements than CSF or neuroimaging biomarkers [9].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Mattsson-Carlgren N, Collij LE, Stomrud E, Pichet Binette A, Ossenkoppele R, Smith R, et al. Plasma biomarker strategy for selecting patients with Alzheimer disease for antiamyloid immunotherapies. JAMA Neurol. 2024;81:69–78. https://doi.org/10.1001/jamaneurol.2023.4596. source

  • Probably not a substantial claim.

    Study design and conductnone given

    Participants were randomized 1:1:1 to receive placebo, or 100 or 300 mg zervimesine, orally, once daily for 6 months.

    “Participants were randomized 1:1:1 to receive placebo, or 100 or 300 mg zervimesine, orally, once daily for 6 months.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Premisecitation

    Increased GFAP is associated with astrogliosis and linked to pathological processes in Alzheimer's disease, particularly amyloid build-up and neuroinflammation.

    “Increased GFAP, associated with astrogliosis, is a hallmark of and linked to pathological processes in Alzheimer’s disease, particularly amyloid build-up, and neuroinflammation [27].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Pereira JB, Janelidze S, Smith R, Mattsson-Carlgren N, Palmqvist S, Teunissen CE, et al. Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer’s disease. Brain. 2021;144:3505–16. https://doi.org/10.1093/brain/awab223. source

  • Probably not a substantial claim.

    Study design and conductreasoning

    The p-tau217 subgroup analysis was pre-specified in the statistical analysis plan for the SHINE trial.

    “This hypothesis was pre-specified in the statistical analysis plan for the SHINE trial using an indirect measure of brain pathology by assessing baseline plasma p-tau217 levels and using the median value to generate “low” and “high” p-tau217 subgroups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    PrPC can bind APP and can alter levels of Aβ40 and Aβ42.

    “Given that PrPC can bind APP and can alter levels of Aβ40 and Aβ42 [38]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Foley AR, Roseman GP, Chan K, Smart A, Finn TS, Yang K, et al. Evidence for aggregation-independent, PrP C -mediated Aβ cellular internalization. Proc Natl Acad Sci. 2020;117:28625–31. https://doi.org/10.1073/pnas.2009238117. source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    The Aβ42/40 ratio is decreased in AD patients reflecting increased brain amyloid plaque load, and has been helpful in the diagnosis of AD.

    “The Aβ42/40 ratio is decreased in AD patients reflecting increased brain amyloid plaque load, and has been helpful in the diagnosis of AD [34, 35].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34] Hansson O, Blennow K, Zetterberg H, Dage J. Blood biomarkers for Alzheimer’s disease in clinical practice and trials. Nat Aging. 2023;3:506–19. https://doi.org/10.1038/s43587-023-00403-3. source
    • cites [35] Lewczuk P, Matzen A, Blennow K, Parnetti L, Molinuevo JL, Eusebi P, et al. Cerebrospinal fluid Aβ42/40 corresponds better than Aβ42 to amyloid PET in Alzheimer’s disease. J Alzheimers Dis. 2016;55:813–22. https://doi.org/10.3233/JAD-160722. source

      Checked before — its earlier verdict is held back until a new check runs.

  • It may state two separate claims as one.

    Interpretationcitation

    Findings from the SHINE p-tau217 subgroup analysis identified a patient population most likely to respond to zervimesine treatment, with favorable findings of a biological impact - decrease in GFAP and trends in decreases in NfL and Aβ42 - consistent with improved clinical outcomes.

    “Findings from the SHINE p-tau217 subgroup analysis identified a patient population most likely to respond to zervimesine treatment, with favorable findings of a biological impact – decrease in GFAP and trends in decreases in NfL and Aβ42 – consistent with improved clinical outcomes [7, 8].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] Cognition Therapeutics. A Study to Evaluate the Safety and Efficacy of CT1812 in Subjects With Mild to Moderate Alzheimer’s Disease. ClinicalTrials.gov identifier: NCT035077. 2025 [cited 2026 Feb 4]. Accessed 4 Feb 2026. https://clinicaltrials.gov/study/NCT03507790.
    • cites [8] Vijverberg EGB, Scharre DW, Woodward M, Catalano S, Hamby ME, Grundman M, et al. Randomized, Double-Blind Study of Zervimesine in Mild to Moderate Alzheimer’s Disease. Journal of Alzheimer's Disease. 2026. https://doi.org/10.1177/13872877261437145. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    Elevated levels of GFAP in plasma and serum are associated with the degree and rate of neurodegeneration, Aβ positivity and cognitive decline in individuals with AD.

    “Elevated levels of GFAP in plasma and serum are associated with the degree and rate of neurodegeneration, Aβ positivity and cognitive decline in individuals with AD [27, 28].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [27] Pereira JB, Janelidze S, Smith R, Mattsson-Carlgren N, Palmqvist S, Teunissen CE, et al. Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer’s disease. Brain. 2021;144:3505–16. https://doi.org/10.1093/brain/awab223. source
    • cites [28] Phillips JM, Winfree RL, Seto M, Schneider JA, Bennett DA, Dumitrescu LC, et al. Pathologic and clinical correlates of region-specific brain GFAP in Alzheimer’s disease. Acta Neuropathol. Springer Science and Business Media Deutschland GmbH; 2024;148. https://doi.org/10.1007/s00401-024-02828-5. source

      Checked before — its earlier verdict is held back until a new check runs.

  • The quote only partly states this claim.

    Interpretationown data

    The trends in reducing plasma Aβ40, Aβ42, and NfL provide support for a role of zervimesine in impacting amyloid biology, neuroinflammation and neurodegeneration in patients with mild to moderate AD that have lower than 1 pg/ml p-tau217 levels at baseline.

    “which provides support for a role of zervimesine in impacting amyloid biology, neuroinflammation and neurodegeneration in patients with mild to moderate AD that have lower than 1 pg/ml p-tau17 levels at baseline using the AlzPath Dx assay.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    Zervimesine modulates Aβ toxicity (CTSS, B2M, LPL, APOA5, PSMA3, PSMB2, PSMAB5, LTF), neuronal trafficking (GRN, IGF2R, CLSTN1, RAB5B, SAA4), and synaptic plasticity (CANX, AP2M1, ACTB).

    “Several biomarkers identified in either or both the mITT population and p-tau217 subgroup analyses, supports that zervimesine modulates i) Aβ toxicity (CTSS, B2M, LPL, APOA5, PSMA3, PSMB2, PSMAB5, LTF), (ii) neuronal trafficking (GRN, IGF2R, CLSTN1, RAB5B, SAA4), and (iii) synaptic plasticity (CANX, AP2M1, ACTB).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    EEA1 is a key marker of early endosomes that plays a crucial role in the endocytic trafficking and amyloidogenic processing of amyloid precursor protein (APP), and altered expression of endosomal proteins including EEA1 can contribute to AD progression, particularly in relation to Aβ accumulation.

    “EEA1 is a key protein is a key marker of early endosomes that plays a crucial role in the endocytic trafficking and amyloidogenic processing of amyloid precursor protein (APP) [42], and altered expression of endosomal proteins including EEA1, can contribute to the AD progression, particularly in relation to Aβ accumulation [43].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] Burrinha T, Martinsson I, Gomes R, Terrasso AP, Gouras GK, Almeida CG. Upregulation of APP endocytosis by neuronal aging drives amyloid-dependent synapse loss. J Cell Sci. 2021. https://doi.org/10.1242/jcs.255752. source
    • cites [43] Xicota L, Lagarde J, Eysert F, Grenier-Boley B, Rivals I, Botté A, et al. Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment. Transl Psychiatry. 2023. https://doi.org/10.1038/s41398-023-02355-z. source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation

    Progranulin (GRN) regulates lysosomal biogenesis, inflammation and stress response, and loss of function mutations or decreased levels increase risk for neurodegenerative diseases including AD.

    “Progranulin (GRN) regulates lysosomal biogenesis, inflammation and stress response [44]. GRN has been genetically linked to the neurodegeneration, with loss of function mutations or decreased levels have increased risk for neurodegenerative diseases including AD [44].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Rhinn H, Tatton N, McCaughey S, Kurnellas M, Rosenthal A, Elsevier Ltd. Progranulin as a therapeutic target in neurodegenerative diseases. Trends Pharmacol Sci. 2022. https://doi.org/10.1016/j.tips.2021.11.015. source

  • It may state two separate claims as one.

    Study design and conductnone given

    Limitations of this study include a limited sample size, and sample sizes were even smaller in subgroups.

    “Limitations of this study include a limited sample size, and sample sizes were even smaller in subgroups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    GPX3 is an enzyme involved in the antioxidant system and its expression is altered in AD.

    “GPX3 is an enzyme involved in the antioxidant system and its expression is altered in AD [49].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Panyard DJ, Reus LM, Ali M, Liu J, Deming YK, Lu Q, et al. Post-GWAS multiomic functional investigation of the TNIP1 locus in Alzheimer’s disease highlights a potential role for GPX3. Alzheimers Dement. 2024;20:5044–53. https://doi.org/10.1002/alz.13848. source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    CLSTN1 plays a role in Aβ processing, axonal transport and formation of synapses.

    “CLSTN plays a role in Aβ processing, axonal transport and formation of synapses [53].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Vagnoni A, Perkinton MS, Gray EH, Francis PT, Noble W, Miller CCJ. Calsyntenin-1 mediates axonal transport of the amyloid precursor protein and regulates aβ production. Hum Mol Genet. 2012;21:2845–54. https://doi.org/10.1093/hmg/dds109. source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim. It may be too vague to check against evidence.

    Interpretationreasoning

    Findings of the SHINE study support the continued clinical development of zervimesine for the treatment of neurodegenerative diseases.

    “In sum, findings of the SHINE study support the continued clinical development of zervimesine for the treatment of neurodegenerative diseases.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Interpretationreasoning

    It is possible that some biomarkers identified may reflect biological changes in the brain, while others may reflect changes occurring in the periphery that may not be disease-relevant.

    “it is possible that while some biomarkers identified may reflect biological changes in the brain, it is also possible that some biomarkers may reflect changes occurring in the periphery, that may not be disease-relevant.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Study design and conductreasoning

    The analysis of GFAP correlations used an unadjusted p-value of p ≤ 0.05, and it is likely that 5% of the proteins may be false-positives.

    “Given this analysis was performed using an unadjusted p-value of p ≤ 0.05, it is likely that 5% of the proteins may be false-positives.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    Plasma proteomic analysis of SHINE participants supports a role of zervimesine in impacting amyloid biology, synaptic biology, vesicle and lipid trafficking, neuroinflammation and neurodegeneration and highlights a newly discovered set of biomarkers to track in future trials, biomarkers which could reflect S2R pathway engagement or an impact on disease progression.

    “Plasma proteomic analysis of SHINE participant further supports a role of zervimesine in impacting amyloid biology, synaptic biology, vesicle and lipid trafficking, neuroinflammation and neurodegeneration and highlights a newly discovered set of biomarkers to track in future trials, biomarkers which could reflect S2R pathway engagement or an impact on the disease progression.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    In a subgroup analysis of the SHINE trial, treatment with zervimesine for 6 months leads to positive changes (decreases) in canonical biomarkers of neuroinflammation, trends towards dampening of neurodegeneration, and an impact on amyloid biology; biological effects consistent with the greater clinical effect size seen in the low p-tau217 subgroup.

    “In a subgroup analysis of the SHINE trial, in alignment with the clinical effects and CSF biomarker changes, treatment with zervimesine for 6 months leads to positive changes (decreases) in canonical biomarkers of neuroinflammation, trends towards dampening of neurodegeneration, and an impact on amyloid biology; biological effects consistent with the greater clinical effect size seen in the low p-”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    CTSG is involved in Aβ deposition and like CTSS can modulate immune responses.

    “and is involved in Aβ deposition and like CTSS can modulate immune responses [50].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Savage MJ, Iqbal M, Loh T, Trusko SP, Scott R, Siman R. Cathepsin G: localization in human cerebral cortex and generation of amyloidogenic fragments from the β-amyloid precursor protein. Neuroscience. 1994;60:607–19. https://doi.org/10.1016/0306-4522(94)90490-1. source

  • It may state two separate claims as one.

    Study design and conductown data

    All proteomics differential abundance and correlations analysis performed considered unadjusted p-values and did not control for multiple comparisons, thus permitting a greater likelihood of type 1 errors (false positives).

    “All proteomics differential abundance and correlations analysis performed considered unadjusted p-values and did not control for multiple comparisons, thus permitting a greater likelihood of type 1 errors (false positives).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    LPL is a key enzyme involved in lipid metabolism; by interacting with lipoprotein receptors such as LDLR, it promotes internalization of lipoproteins, contributing to lipid homeostasis and receptor-mediated signaling in neurons; and it maintains membrane composition and fluidity necessary for synaptic function and neurotransmitter release.

    “Of note, LPL is a key enzyme involved in lipid metabolism. By interacting with lipoprotein receptors, such as the direct interactor with S2R (TMEM97), LDLR [46], LPL promotes the internalization of lipoproteins, contributing to lipid homeostasis and receptor-mediated signaling in neurons. In addition, LPL maintains the balance of membrane composition and fluidity, which is crucial for proper”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [46] Riad A, Zeng C, Weng C-C, Winters H, Xu K, Makvandi M, et al. Sigma-2 receptor/TMEM97 and PGRMC-1 increase the rate of internalization of LDL by LDL receptor through the formation of a ternary complex. Sci Rep. 2018;8:16845. https://doi.org/10.1038/s41598-018-35430-3. source
    • cites [47] Althaher AR, S. AL Shehadeh R. Lipoprotein Lipase and Neurological Health: Investigating its Impact on Brain Function and Alzheimer’s Disease. Open Biomark J. 2024;14. https://doi.org/10.2174/0118753183367402241216115139. source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductnone given

    The p-tau217 subgroup analysis was prespecified but was not the primary analysis.

    “While the p-tau217 subgroup analysis was prespecified, it was not the primary analysis.”
    Quote in the paperNot a substantial claim
38 of 38

  • The paper relies on this without support.

    Zervimesine is a modulator of the sigma-2 receptor (S2R/TMEM97).

    “Zervimesine (CT1812) is an orally administered small molecule modulator of the sigma-2 receptor (S2R/TMEM97) in clinical development for treatment of Alzheimer’s disease (AD; NCT03507790; NCT05531656) and dementia with Lewy bodies (DLB; NCT05225415).”

  • The paper relies on this without support.

    GFAP is a neuroinflammatory biomarker.

    “the neuroinflammatory marker GFAP”

  • The paper relies on this without support.

    NfL is a recognized biomarker of neurodegeneration for multiple neurodegenerative disorders, including AD, in which CSF levels are elevated relative to healthy non-demented control.

    “NfL is a recognized biomarker of neurodegeneration for multiple neurodegenerative disorders, including AD, in which CSF levels are elevated relative to healthy non-demented control.”

  • The paper relies on this without support.

    HSPA5 and HSP90AB1 are members of the heat shock protein family and as chaperone proteins are involved in controlling protein folding and ER homeostasis.

    “HSPA5, HSP90AB1are both members of the heat shock protein family and as chaperone proteins are involved in controlling protein folding and ER homeostasis.”

  • The paper relies on this without support.

    Elevated secreted GFAP levels is a well-established marker of astrogliosis, detectable in plasma due to blood-brain-barrier disruption, and elevated in plasma of patients with AD.

    “Elevated secreted GFAP levels is a well-established marker of astrogliosis, detectable in plasma due to blood-brain-barrier disruption, and elevated in plasma of patients with AD.”
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.

  • Conflicting differential-abundance threshold for the 15 GFAP correlates

    Minor

    The results say the 15 proteins met a differential-abundance threshold of p ≤ 0.10, while the discussion describes the same 15 as meeting p < 0.05. The stricter threshold is not supported by the reported comparison.

1 of 1

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 7

  1. Ashton NJ, Brum WS, Molfetta GD, Benedet AL, Arslan B, Jonaitis E, et al. Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology. JAMA Neurol. 2024;81:255–63. https://doi.org/10.1001/jamaneurol.2023.5319. · DOI · Paper page
  2. Sperling RA, Selkoe DJ, Reyderman L, Cao Y, van Dyck CH. Does the Current Evidence Base Support Lecanemab Continued Dosing for Early Alzheimer’s Disease? [Perspectives Session]. Alzheimer’s Assoc Int Conf. Philadelphia, PA; 2024.
  3. Cognition Therapeutics. Cognition Therapeutics Study of Zervimesine (CT1812) in Early Alzheimer’s Disease Surpasses 50% Enrollment Target [Press Release]. 2025 Jul 1; https://ir.cogrx.com/press_releases/cognition-therapeutics-study-of-zervimesine-ct1812-in-early-alzheimers-disease-surpasses-50-enrollment-target/.
  4. Cognition Therapeutics. Cognition Therapeutics’ Analysis Correlates Biomarker Changes with Cognitive Benefit in Alzheimer’s Population [Press Release]. 2024 Nov 25; https://ir.cogrx.com/press_releases/cognition-therapeutics-analysis-correlates-biomarker-changes-with-cognitive-benefit-in-alzheimers-population/.
  5. Cognition Therapeutics. Cognition Therapeutics presents phase 3 plan for zervimesine (CT1812) in Alzheimer’s disease at Clinical Trials on Alzheimer’s Disease (CTAD) conference. [Press Release]. 2025 Dec 1; https://ir.cogrx.com/press_releases/cognition-therapeutics-presents-phase-3-plan-for-zervimesine-ct1812-in-alzheimers-disease-at-clinical-trials-on-alzheimers-disease-ctad-conference/.
  6. Lilly. Results from Lilly’s Landmark Phase 3 Trial of Donanemab Presented at Alzheimer’s Association Conference and Published in JAMA [Press Release]. 2023 Jul 17; https://investor.lilly.com/news-releases/news-release-details/results-lillys-landmark-phase-3-trial-donanemab-presented.
  7. Eisai. New Clinical Data Demonstrates Three Years of Continuous Treatment with Dual-Acting LEQEMBI® (lecanemab-irmb) Continues to Significantly Benefit Early Alzheimer’s Disease Patients Presented at AAIC 2024. [Press Release]. 2024. https://www.eisai.com/news/2024/news202456.html.

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Metadata

Authors
Di Caro, V., Cho, E., Thiel, J., Lizama, B. N., Koel-Simmelink, M. J. A., Pandey, K., Duong, D., Seyfried, N. T., Grundman, M., Teunissen, C. E., Zetterberg, H., Blennow, K., Caggiano, A. O., & Hamby, M. E.
Affiliations
  • Cognition Therapeutics (United States) (US)
  • Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
  • Emory University (US)
  • University of California San Diego (US)
  • University of Wisconsin–Madison (US)
  • Sahlgrenska University Hospital (SE)
Corresponding author
Hamby, Mary E.
ORCID
Venue
Alzheimer's Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2026-04-06
Volume
18
Issue
1
ISSN
1758-9193 (ISSN-L)
DOI
10.1186/s13195-026-02025-4
PMC
PMC13182022
OpenAlex
W7151006868
Cited by
1
References
44
Citations by year
2026: 1
FWCI
1.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s Research & Therapy (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Pure Amsterdam UMC (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute on Aging (1R01AG058660)
  • Alzheimer's Drug Discovery Foundation
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
Keywords
Alzheimer's disease, sigma-2 receptor, TMEM97, neuroinflammation, glial fibrillary acidic protein, plasma biomarkers, phosphorylated tau, amyloid-beta, neurofilament light chain, pharmacodynamic biomarkers, dementia with Lewy bodies, amyloid-beta binding, lipid metabolism, immune response, SHINE trial
MeSH terms
Neuroinflammatory Diseases, Aged, Alzheimer Disease, Double-Blind Method, Female, Glial Fibrillary Acidic Protein, Humans, Male, Biomarkers, Amyloid beta-Peptides, Proteomics

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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.

A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

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