Evidence map›Paper›PMID 40317057›Full record

Trial reportAlzheimer's research & therapy2025

Prognostic value of plasma biomarkers for informing clinical trial design in mild-to-moderate Alzheimer's disease.

Yuqi Qiu, Diane M Jacobs, Karen Messer, David P Salmon, Cheryl L Wellington, Sophie Stukas, Carolyn Revta, James B Brewer, Gabriel C Léger, Brianna Askew and 6 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03605667 (A Phase 2 Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Efficacy and Safety of BHV-4157 in Patients With Mild to Moderate Alzheimer's Disease), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03605667 phase2completednot on this map

A Phase 2 Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Efficacy and Safety of BHV-4157 in Patients With Mild to Moderate Alzheimer's Disease

TypeinterventionalSponsorBiohaven Pharmaceuticals, Inc.Ran2018 to 2021Enrolled350ConditionsAlzheimer DiseaseArmstroriluzole, Placebo oral capsule
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Yuqi Qiu *KLATASDS-MOE, School of Statistics, East China Normal University, Shanghai, China.
Diane M Jacobs *Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA. djacobs@ucsd.edu.
Karen MesserDivision of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health, University of California San Diego, La Jolla, CA, USA.
David P SalmonDepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Cheryl L WellingtonDepartment of Pathology and Laboratory Medicine, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
Sophie StukasDepartment of Pathology and Laboratory Medicine, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
Carolyn RevtaAlzheimer's Disease Cooperative Study, University of California San Diego, La Jolla, CA, USA.
James B BrewerDepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Gabriel C LégerDepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Brianna AskewAlzheimer's Disease Cooperative Study, University of California San Diego, La Jolla, CA, USA.
Lia DonahueBiohaven Pharmaceuticals, Inc, New Haven, CT, USA.
Stephen KaplitaBiohaven Pharmaceuticals, Inc, New Haven, CT, USA.
Vladimir CoricBiohaven Pharmaceuticals, Inc, New Haven, CT, USA.
Irfan A QureshiBiohaven Pharmaceuticals, Inc, New Haven, CT, USA.
Howard H FeldmanDepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Alzheimer’s Disease Cooperative Study T2 Protect AD Study Group

Funding

RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOUGLAS R GALASKO · 2019 to 2026
$34.9M
Research Education ComponentP30AG066518 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI KEVIN M DUFF, Lisa C Silbert · 2020 to 2026
$28.6M
NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG066518NIA NIH HHS U19 AG010483
6 · The paper itself

Abstract

backgroundEmerging evidence supports the diagnostic and prognostic utility of plasma biomarkers in Alzheimer's disease (AD), particularly in early disease stages. We sought to extend these findings by evaluating the prognostic value of plasma biomarkers in a clinical trial of mild-to-moderate AD.

methodsPost-hoc analyses investigated whether baseline concentrations of plasma biomarkers (Aβ42/Aβ40, T-tau, P-tau181, NfL, and GFAP) predicted change in ADAS-Cog11, CDR-SB, and volumetric MRI among participants in T2 Protect AD, a negative 48-week, phase-2, placebo-controlled trial of troriluzole in mild-to-moderate AD. All trial participants met diagnostic criteria for probable AD. Baseline concentrations of, and 48-week changes in, plasma biomarkers were assessed for association with 48-week change in outcomes using linear regression. Combinations of baseline biomarkers that best predicted change on the ADAS-Cog11 and CDR-SB were identified using least absolute shrinkage and selection operator (LASSO) regression. Biomarker-informed sample size calculations were modeled.

resultsOf 350 trial participants, 319 had all requisite biomarker and clinical outcome data for inclusion in these analyses (mean age 71.5, SD = 8.03; 58.6% female). Higher plasma NfL at baseline predicted worsening scores on the ADAS-Cog11 (effect size (ES) = 1.42, 95%CI = [0.43, 2.41], p = 0.026) and CDR-SB (ES = 0.42, 95%CI = [0.10, 0.73], p = 0.048). LASSO regression revealed that worsening on the ADAS-Cog11 was best predicted by the combination of baseline plasma NfL, T-tau, and Aβ42/40 ratio, whereas baseline NfL alone best predicted worsening on CDR-SB. Higher baseline NfL predicted increasing ventricular volume (ES = 1.30cm

conclusionsElevated baseline plasma NfL predicted more rapid clinical decline and MRI volume loss. Furthermore, increasing plasma NfL concentration over time was associated with worsening on the CDR-SB. Plasma NfL is an easily accessible biomarker that may enhance the design of clinical trials in mild-to-moderate AD.

trial registrationThe T2 Protect AD trial was registered as NCT03605667 on clinicaltrials.gov on 2018-07-27.

Indexed as

Alzheimer DiseaseBiomarkersAgedAged, 80 and overAmyloid beta-PeptidesDouble-Blind MethodFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedPrognosisResearch Designtau ProteinsAmyloid beta-PeptidesBiomarkerstau Proteins

Identifiers

PMID40317057
PMCPMC12046789

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.