ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Plasma GFAP for populational enrichment of clinical trials in preclinical Alzheimer's disease.
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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10citing papers in PubMed, 1 pooled it
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Plasma Biomarkers for Alzheimer's Disease Across the Continuum: A Systematic Review of SIMOA-Based Studies.Cellular and molecular neurobiology · 2026Pooled it
- Differential associations of plasma biomarkers with Alzheimer's disease and small vessel disease: A multimodal imaging study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Astrocytes in Brain Aging and Neurodegeneration: Cellular Mechanisms and Interventional Strategies.Journal of neurochemistry · 2026Review
- Observational
- Nutritional substrates and microglial metabolic fitness in brain aging and Alzheimer's disease: from lipid handling to TREM2-linked translation.Frontiers in nutrition · 2026Review
- Linking Cell Architecture to Mitochondrial Signaling in Neurodegeneration: The Role of Intermediate Filaments.International journal of molecular sciences · 2025Review
- Neuroimaging correlates and biomarker performance of a fully automated plasma p-tau217/Aβ42 ratio assay in a clinical cohort with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Head-to-head comparison of plasma p-tau217 immunoassays for incipient Alzheimer's disease in community cohorts.Research square · 2025Article
- Head-to-head comparison of plasma p-tau217 immunoassays for incipient Alzheimer's disease in community cohorts.medRxiv : the preprint server for health sciences · 2025Article
- Plasma GFAP for populational enrichment of clinical trials in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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Authors and funding
37 authors.
Bruna BellaverDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Guilherme PovalaDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Pamela C L FerreiraDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Guilherme Bauer-NegriniDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Firoza Z LussierDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Douglas T LeffaDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
João Pedro Ferrari-SouzaGraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Matheus S RodriguesDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Livia AmaralDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Markley S OliveiraDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Carolina SoaresDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Andreia RochaDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Pampa SahaDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Nesrine RahmouniTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Quebec, Canada.
Arthur MacedoTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Quebec, Canada.
Cécile TissotTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Quebec, Canada.
Joseph TherriaultTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Quebec, Canada.
Stijn ServaesTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Quebec, Canada.
Jesse KlostranecTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Quebec, Canada.
Maxime MontembeaultTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Quebec, Canada.
Andréa L BenedetDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Rebecca Langhough KoscikWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Tobey J BetthauserWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Brad T ChristianWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Rachael WilsonWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Gallen Triana-BaltzerNeuroscience Biomarkers, Janssen Research and Development, La Jolla, California, USA.
Paolo VitaliTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Quebec, Canada.
Serge GauthierTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Quebec, Canada.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Thomas K KarikariDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Dana TudorascuDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Eduardo R ZimmerGraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Sterling JohnsonWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Pedro Rosa-NetoTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Quebec, Canada.
Tharick A PascoalDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.ORCID 0000-0001-9057-8014
Funding
Vascular Moderators of the Impact of Alzheimer's Pathology in the Young-OldP01AG025204 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Milos D Ikonomovic · 2005 to 2026
$56.5MLongitudinal multicenter head-to-head harmonization of tau PET tracersR01AG073267 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAKER, SUZANNE L, PASCOAL, THARICK · 2021 to 2025
$41.1MWisconsin Registry for Alzheimer's Prevention: Sex Differences in DNA MethylationR01AG027161 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Nathaniel Ark Chin, Sterling C Johnson · 2007 to 2026
$35.6MThe Longitudinal Course of Neural Function and Amyloid in People At Risk for ADR01AG021155 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sterling C Johnson · 2004 to 2026
$27.0MWisconsin Registry for Alzheimer's PreventionRF1AG027161 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI JOHNSON, STERLING C · 2018 to 2018
$18.8MPlasma brain-derived tau: a novel Alzheimer’s disease-type neurodegeneration biomarker with potential to complete the AT(N) scheme in bloodR01AG083874 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Thomas K Karikari · 2023 to 2026
$14.5MHead-to-head comparisons of high-performance plasma phospho-tau epitopes for the detection of Alzheimer's diseaseR01AG075336 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Tharick Pascoal · 2022 to 2026
$3.7MAgneta Prytz-Folkes & Gösta Folkes Foundation #2020-00124Aina (Ann) WallströmsALF-agreement #ALFGBG-715986ALF-agreement #ALFGBG-965240Alzheimerfonden #AF-930627Alzheimer's Association AARFD-24-1307995Anna Lisa and Brother Björnsson's Foundation #2019-02397Anna Lisa and Brother Björnsson's Foundation #2022-01018Anna Lisa and Brother Björnsson's Foundation #2023-00356Brain Canada Foundation 33397Brain Canada Foundation CFI Project 34874Brazilian National Institute of Science and Technology in Excitotoxicity and Neuroprotection 465671/2014-4BrightFocus Foundation #A2020812FCanadian Consortium of Neurodegeneration and Aging CCNA; MOP-11-51-31-team 1Chercheur Boursier 2020-VICO-279314Chercheur Boursier 2024-VICO-356138Chercheur Boursier AG021155Chercheur Boursier AG027161CIHR 159815CIHR 162303CIHR MOP-11-51-31CIHR RFN 152985County CouncilsEuropean Union Joint Program for Neurodegenerative Disorders JPND2019-466-236European Union Joint Program for Neurodegenerative Disorders SG-23-1038904 QCEuropean Union Joint Program for Neurodegenerative Disorders ZEN-21-848495European Union Joint Programme - Neurodegenerative Disease Research JPND2021-00694European Union's Horizon Europe research 101053962European Union's Horizon Europe research #201809-2016862European Union's Horizon Europe research #ADSF-21-831376-CEuropean Union's Horizon Europe research #ADSF-21-831377-CEuropean Union's Horizon Europe research #ADSF-21-831381-CEuropean Union's Horizon Europe research #ADSF-24-1284328-CEuropean Union's Horizon Europe research #ALFGBG-71320Familjen Rönströms StiftelseFonds de Recherche du Québec - Santé 2020-VICO-279314Fonds de Recherche du Québec-Santé 2020-VICO-279314Fonds de Recherche du Québec-Santé 24AARFD-1243899Fonds de Recherche du Québec-Santé 5 P01 AG025204-17Fonds de Recherche du Québec-Santé AARFD-22-923814Fonds de Recherche du Québec-Santé AARFD-22-974627Fonds de Recherche du Québec-Santé AARFD-24-1307995Fonds de Recherche du Québec-Santé AARFD-24-1313939Gamla Tjänarinnor FoundationGun and Bertil Stohnes FoundationHjärnfonden #FO2020-0240Instituto Serrapilheira #2021-03244Instituto Serrapilheira #AARF-21-850325Instituto Serrapilheira AARF-D-231150249Instituto Serrapilheira ALZ-NAN-22-928381Instituto Serrapilheira Serra-1912-31365International Society for Neurochemistry's Career Development GrantKirsten and Freddy Johansen Foundation 312306/2021-0Kirsten and Freddy Johansen Foundation 312410/20182Kirsten and Freddy Johansen Foundation 409066/2022-2Kirsten and Freddy Johansen Foundation 435642/2018-9Mary-Ann Sjöbloms FoundationNational Institute in Aging 5R01AG073267National Institute in Aging 5R01AG075336National Institute of Health and Care Research UKDRI-1003NIA NIH HHS AG021155NIA NIH HHS P01 AG025204NIA NIH HHS R01 AG021155NIA NIH HHS R01 AG027161NIA NIH HHS R01 AG073267NIA NIH HHS R01 AG075336NIA NIH HHS R01 AG083874NIA NIH HHS RF1 AG027161Olav Thon FoundationStiftelsen för Gamla Tjänarinnor #FO2022-0270Swedish Alzheimer Foundation #AF-930351Swedish Alzheimer Foundation #AF-939721Swedish Alzheimer Foundation #AF-968270Swedish Alzheimer Foundation #AF-994551Swedish Alzheimer Foundation #ALZ2022-0006Swedish Alzheimer Foundation #FO2017-0243Swedish Dementia FoundationSwedish governmentSwedish Parkinson FoundationSwedish Research Council #2017-00915Swedish Research Council #2022-00732Weston Brain Institute
Abstract
introductionCognitively unimpaired (CU) amyloid beta (Aβ)+ individuals with elevated plasma glial fibrillary acidic protein (GFAP) have an increased risk of Alzheimer's disease (AD)-related progression. We tested the utility of plasma GFAP for population enrichment CU populations in clinical trials.
methodsWe estimated longitudinal progression, effect size, and costs of hypothetical clinical trials designed to test an estimated 25% drug effect on reducing tau positron emission tomography (PET) accumulation in the medial temporal lobe (MTL) and temporal neocortical region (NEO-T).
resultsCU GFAP+/Aβ+ individuals present an increased annual rate of change and effect size in tau PET DISCUSSION: Our results suggest that clinical trials focusing on preclinical AD recruiting Aβ+ individuals with elevated GFAP levels would improve cost effectiveness. HIGHLIGHTS: Cognitively unimpaired (CU) glial fibrillary acidic protein (GFAP)+/amyloid beta (Aβ)+ shows increased changes in tau positron emission tomography (PET) . CU GFAP+/Aβ+ enriched clinical trials require a reduced sample size compared to Aβ+ only. CU GFAP+/Aβ+ enrichment reduces Aβ PET scans required and costs. CU GFAP+/Aβ+ enrichment allows the selection of individuals at early stages of the Alzheimer's disease continuum.
Indexed as
Alzheimer DiseaseClinical Trials as TopicGlial Fibrillary Acidic ProteinAgedAmyloid beta-PeptidesBiomarkersDisease ProgressionFemaleHumansLongitudinal StudiesMalePositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesBiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteintau Proteinsclinical trial enrichmentglial fibrillary acidic proteinpositron emission tomography imagingpreclinical Alzheimer's diseasetau deposition
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