Evidence map›Paper›PMID 37932961›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Plasma Aβ42/Aβ40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease.

Robert A Rissman, Oliver Langford, Rema Raman, Michael C Donohue, Sara Abdel-Latif, Matthew R Meyer, Traci Wente-Roth, Kristopher M Kirmess, Jennifer Ngolab, Charisse N Winston and 11 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04468659 (AHEAD 3-45 Study), which is not on this map. Cited by 103 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 4 pooled it
29.6field-weighted citation impact, top 1% of its field
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.

NCT04468659 phase3active not recruitingnot on this map

AHEAD 3-45 Study: A Placebo-Controlled, Double-Blind, Parallel-Treatment Arm, 216 Week Study With an Extension Phase to Evaluate Efficacy and Safety of Treatment With BAN2401 in Subjects With Preclinical Alzheimer's Disease and Elevated Amyloid (A45 Trial) and in Subjects With Early Preclinical Alzheimer's Disease and Intermediate Amyloid (A3 Trial)

TypeinterventionalSponsorEisai Inc.Ran2020 to 2031Enrolled1,400ConditionsPreclinical Alzheimer's Disease, Early Preclinical Alzheimer's DiseaseArmsLecanemab, Placebo
3 · Its place in the literature

Who cites it

103 citing papers in PubMed, 4 syntheses or guidelines pooled it, 133 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Pooled it
  4. Pooled it
  5. Trial
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  9. Gamma sensory stimulation in mild Alzheimer's dementia: An open-label extension study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  10. Article
  11. More efficient screening for preclinical Alzheimer's clinical trials using mixture of experts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  12. Article
  13. Exploring longitudinal relationships among Alzheimer's disease biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  14. Observational
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  17. Review
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43 more citing papers are in PubMed but not listed here.

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

21 authors at 4 institutions in 1 country.

Robert A RissmanDepartment of Neurosciences, University of California San Diego, La Jolla, California, USA.ORCID 0000-0001-9245-8278
Oliver LangfordAlzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA.
Rema RamanAlzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA.
Michael C DonohueAlzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA.
Sara Abdel-LatifAlzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA.
Matthew R MeyerC2N Diagnostics, St. Louis, Missouri, USA.
Traci Wente-RothC2N Diagnostics, St. Louis, Missouri, USA.
Kristopher M KirmessC2N Diagnostics, St. Louis, Missouri, USA.
Jennifer NgolabAlzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA.
Charisse N WinstonDepartment of Neurosciences, University of California San Diego, La Jolla, California, USA.
Gustavo Jimenez-MaggioraAlzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA.
Michael S RafiiAlzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA.
Pallavi SachdevEisai US, Nutley, New Jersey, USA.
Tim WestC2N Diagnostics, St. Louis, Missouri, USA.
Kevin E YarasheskiC2N Diagnostics, St. Louis, Missouri, USA.
Joel B BraunsteinC2N Diagnostics, St. Louis, Missouri, USA.
Michael IrizarryEisai US, Nutley, New Jersey, USA.
Keith A JohnsonBrigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Paul S AisenAlzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA.
Reisa A SperlingBrigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
AHEAD 3-45 Study team
University of Southern California · USC2N Diagnostics (United States) · USBrigham and Women's Hospital · USEisai (United States) · US

Funding

The Alzheimer's Clinical Trial Consortium - Down Syndrome Network (ACTC- DSN)U24AG057437 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Paul S. Aisen, RONALD C PETERSEN · 2018 to 2026
$198.4M
The Health & Aging Brain Study - Health Disparities (HABS-HD)U19AG078109 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI Sid E O'Bryant · 2022 to 2026
$181.1M
Health and Aging Brain among Latino Elders (HABLE-AT(N)) StudyR01AG058533 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI JOHNSON, LEIGH A, O'BRYANT, SID E · 2020 to 2025
$45.4M
Combination anti-amyloid therapy for preclinical Alzheimer's diseaseR01AG061848 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI AISEN, PAUL S., JOHNSON, KEITH A. · 2018 to 2024
$43.9M
Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's DiseaseR01AG053798 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI AISEN, PAUL S., CUMMINGS, JEFFREY L. · 2017 to 2022
$39.4M
The VETSA Longitudinal Twin Study of Cognition and Aging (VETSA 4)R01AG050595 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELMAN, JEREMY A, FRANZ, CAROL ELAINE · 2015 to 2024
$28.0M
USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Robert Rissman · 2020 to 2026
$27.8M
The A3 Study: Ante-Amyloid Prevention of Alzheimer's diseaseR01AG054029 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI AISEN, PAUL S., JOHNSON, KEITH A. · 2016 to 2023
$20.9M
B-Synuclein as a Treatment for Lewy Body DiseaseR01AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT · 2001 to 2021
$5.2M
A Blood Test for Screening Into Alzheimer's Prevention TrialsR01AG058252 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI O'BRYANT, SID E, RISSMAN, ROBERT · 2017 to 2021
$3.2M
a-synuclein clearance strategies for the treatment of Lewy body disease.R37AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MASLIAH, ELIEZER · 2006 to 2014
$2.7M
Precision Medicine for Inflammatory Treatment for Alzheimer's Disease in Down SyndromeRF1AG073979 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RAFII, MICHAEL S, RISSMAN, ROBERT · 2021 to 2022
$2.6M
NIA NIH HHS K99 AG070390NIA NIH HHS P30 AG066530NIA NIH HHS R01 AG018440NIA NIH HHS R01 AG050595NIA NIH HHS R01 AG053798NIA NIH HHS R01 AG054029NIA NIH HHS R01 AG058252NIA NIH HHS R01 AG058533NIA NIH HHS R01 AG061848NIA NIH HHS R01 AG073979NIA NIH HHS R37 AG018440NIA NIH HHS R44 AG059489NIA NIH HHS R56 AG058533NIA NIH HHS RF1 AG073979NIA NIH HHS U19 AG078109NIA NIH HHS U24 AG057437NINDS NIH HHS R25 NS117367
6 · The paper itself

Abstract

introductionIncorporating blood-based Alzheimer's disease biomarkers such as tau and amyloid beta (Aβ) into screening algorithms may improve screening efficiency.

methodsPlasma Aβ, phosphorylated tau (p-tau)181, and p-tau217 concentration levels from AHEAD 3-45 study participants were measured using mass spectrometry. Tau concentration ratios for each proteoform were calculated to normalize for inter-individual differences. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker against amyloid positivity, defined by > 20 Centiloids. Mixture of experts analysis assessed the value of including tau concentration ratios into the existing predictive algorithm for amyloid positron emission tomography status.

resultsThe area under the receiver operating curve (AUC) was 0.87 for Aβ42/Aβ40, 0.74 for phosphorylated variant p-tau181 ratio (p-tau181/np-tau181), and 0.92 for phosphorylated variant p-tau217 ratio (p-tau217/np-tau217). The Plasma Predicted Centiloid (PPC), a predictive model including p-tau217/np-tau217, Aβ42/Aβ40, age, and apolipoprotein E improved AUC to 0.95. DISCUSSION: Including plasma p-tau217/np-tau217 along with Aβ42/Aβ40 in predictive algorithms may streamline screening preclinical individuals into anti-amyloid clinical trials. CLINICALTRIALS: gov Identifier: NCT04468659 HIGHLIGHTS: The addition of plasma phosphorylated variant p-tau217 ratio (p-tau217/np-tau217) significantly improved plasma biomarker algorithms for identifying preclinical amyloid positron emission tomography positivity. Prediction performance at higher NAV Centiloid levels was improved with p-tau217/np-tau217. All models generated for this study are incorporated into the Plasma Predicted Centiloid (PPC) app for public use.

Indexed as

Alzheimer DiseaseAmyloidAmyloid beta-PeptidesBiomarkersHumansPeptide FragmentsPositron-Emission Tomographytau ProteinsAmyloidAmyloid beta-PeptidesBiomarkersPeptide Fragmentstau Proteinsblood-based biomarkersmass spectrometryplasmatau

Identifiers

PMID37932961
PMCPMC10916957
OpenAlexW4388461419

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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.