ArticleNature medicine2023
Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease.
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Article in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers, 4 of them syntheses that pooled it.
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219citing papers in PubMed, 4 pooled it
51.5field-weighted citation impact, top 1% of its field
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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.
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Who cites it
219 citing papers in PubMed, 4 syntheses or guidelines pooled it, 294 citations in OpenAlex.
- Potential beneficial effects of PD-1/PD-L1 blockade in Alzheimer's disease: a systematic review and meta-analysis of preclinical and clinical studies.Molecular psychiatry · 2026Pooled it
- Neuroinflammatory fluid biomarkers in patients with Alzheimer's disease: a systematic literature review.Molecular psychiatry · 2025Pooled it
- Exploiting blood-based biomarkers to align preclinical models with human traumatic brain injury.Brain : a journal of neurology · 2025Pooled it
- Blood Astrocyte Biomarkers in Alzheimer Disease: A Systematic Review and Meta-Analysis.Neurology · 2024Pooled it
- Matrix metalloproteinase-9 is associated with CX3CL1 on tau and amyloid biomarker pathways in APOE4 carriers.Neurobiology of disease · 2026Trial
- Inhibition of p38α MAPK increases short-term astrocyte reactivity: the exploratory VIP trial in early Alzheimer's disease.Journal of neuroinflammation · 2025Trial
- Low-dose interleukin-2 in patients with mild to moderate Alzheimer's disease: a randomized clinical trial.Alzheimer's research & therapy · 2025Trial
- evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.Alzheimer's research & therapy · 2025Trial
- In vivo multimodal PET/MRI imaging and plasma biomarkers implicate glymphatic dysfunction linking neuroinflammation to tau pathology in the early Alzheimer's disease continuum.European journal of nuclear medicine and molecular imaging · 2026Article
- Elevated endogenous glucagon-like peptide-1 as a novel Alzheimer's disease biomarker associated with neuroinflammation and Aβ pathology.General psychiatry · 2026Article
- Associations between plasma biomarker levels and quantitative postmortem neuropathologic measures in Alzheimer's disease and related dementias.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Extracellular CIRP induces neurotoxic astrocytes via TREM-1 in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Early Spatial and Contextual Coding Deficits in Hippocampal CA1 Precede Performance Decline in an Alzheimer's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synergistic association of insomnia and anxiety with cognitive impairment and dementia in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Engineered Alzheimer Organoids Validate the Link Between Intracellular and Soluble p-Tau Biomarkers and Highlight the Contribution of Astrocytic Tau.Neuroscience bulletin · 2026Article
- Alzheimer's Disease as a Multi-Layer Network Disorder: A Systems Biology Framework Integrating Multi-Omics Mechanisms.Biomedicines · 2026Review
- Classification accuracies of plasma ptau217 vs. ptau217/Aβ1-42 for brain Aβ pathology in cognitively normal older adults.GeroScience · 2026Observational
- Astrocyte reactivity across the AD continuum measured by [European journal of nuclear medicine and molecular imaging · 2026Article
- Astrocyte reactivity modifies the effects of locus coeruleus norepinephrine-related dysfunction on tau and its impact on cognition.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Edentulism, blood-based neurodegenerative biomarkers, and 10-year dementia risk: A mediation analysis in a nationally representative United States cohort.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
159 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
33 authors at 10 institutions in 6 countries.
Bruna BellaverDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-2212-3373
Guilherme PovalaDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-2023-6569
Pamela C L FerreiraDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-2134-9829
João Pedro Ferrari-SouzaDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Douglas T LeffaDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Firoza Z LussierDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Andréa L BenedetDepartment of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Gallen Triana-BaltzerNeuroscience Biomarkers, Janssen Research and Development, La Jolla, CA, USA.
Hartmuth C KolbNeuroscience Biomarkers, Janssen Research and Development, La Jolla, CA, USA.
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; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0003-2711-3833
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; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-7826-4781
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; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Jenna StevensonTranslational 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; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
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; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Oscar L LopezDepartment of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-8546-8256
Dana L TudorascuDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Victor L VillemagneDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Milos D IkonomovicDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
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; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Eduardo R ZimmerGraduate Program in Biological Sciences-Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.ORCID http://orcid.org/0000-0003-3930-4354
Kaj BlennowDepartment of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.ORCID http://orcid.org/0000-0002-1890-4193
Howard J AizensteinDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
William E KlunkDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Beth E SnitzDepartment of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Pauline MakiDepartment of Psychiatry, University of Illinois, Chicago, IL, USA.
Rebecca C ThurstonDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-6580-1202
Ann D CohenDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Mary GanguliDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Thomas K KarikariDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 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; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0001-9116-1376
Tharick A PascoalDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA. pascoalt@upmc.edu.ORCID http://orcid.org/0000-0001-9057-8014
University of Pittsburgh · USDouglas Mental Health University Institute · CAUniversidade Federal do Rio Grande do Sul · BRJanssen (United States) · USKing's College London · GBMontreal Neurological Institute and Hospital · CASahlgrenska University Hospital · SEUniversity of Gothenburg · SEUniversity of Illinois Chicago · USUniversity of Wisconsin–Madison · US
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
$41.1MTAU, AB, SYNUCLEIN AND NITRATIVE/OXIDATIVE DAMAGE IN MCIP01AG014449 · NIA · UNIVERSITY OF PITTSBURGH · PI IKONOMOVIC, MILOS D · 1997 to 2024
$39.7MResearch Education ComponentP30AG066468 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HOWARD J AIZENSTEIN · 2020 to 2026
$29.4MMild Cognitive Impairment: A Prospective Community StudyR37AG023651 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Carmen Andreescu, MARY GANGULI · 2021 to 2026
$18.2MSubclinical vascular disease and AD pathology in the transition from midlife to old ageRF1AG052525 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOPEZ, OSCAR L., REIS, STEVEN E · 2018 to 2018
$9.3MRoles of Gray Matter Brain Aging and Small Vessel Disease in AD PathophysiologyRF1AG025516 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AIZENSTEIN, HOWARD J, VILLEMAGNE, VICTOR LUIS · 2014 to 2021
$9.0MMenopausal Vasomotor Symptoms and Brain Aging in WomenRF1AG053504 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MAKI, PAULINE M, THURSTON, REBECCA C · 2016 to 2019
$4.1MMenopausal Vasomotor Symptoms and Brain Aging in WomenR01AG053504 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MAKI, PAULINE M, THURSTON, REBECCA C · 2021 to 2025
$3.8MHead-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
$3.7MRole of midlife cardiovascular disease on Alzheimer’s Pathology and cerebrovascular reactivity in the young-old.R01AG052446 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COHEN, ANN D. · 2016 to 2020
$3.7MAlzheimer neuroimaging-biomarkers in pre-clinical cognitive decline from a population-based studyR01AG052521 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SNITZ, BETH · 2016 to 2020
$3.3MNHLBI NIH HHS K24 HL123565NHLBI NIH HHS R01 HL105647NIA NIH HHS P01 AG014449NIA NIH HHS P01 AG025204NIA NIH HHS P30 AG066468NIA NIH HHS R01 AG052446NIA NIH HHS R01 AG052521NIA NIH HHS R01 AG052528NIA NIH HHS R01 AG053504NIA NIH HHS R01 AG073267NIA NIH HHS R01 AG075336NIA NIH HHS R37 AG023651NIA NIH HHS RF1 AG025516NIA NIH HHS RF1 AG052525NIA NIH HHS RF1 AG053504
Abstract
An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of Aβ with tau phosphorylation in CU individuals. We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast
Indexed as
Alzheimer DiseaseCognitive DysfunctionAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAstrocytesBiomarkersCross-Sectional StudiesHumansPositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAPP protein, humanBiomarkersMAPT protein, humantau Proteins
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