ArticleNature communications2025
CSF total tau as a proxy of synaptic degeneration.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6citing papers in PubMed
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Who cites it
6 citing papers in PubMed.
- Machine Learning and Multimodal Biomarker Discovery in Alzheimer's Disease.Brain sciences · 2026Review
- Tau-mediated Mechanisms in Alzheimer's Disease Pathogenesis.Molecular neurobiology · 2026Review
- Autoimmune Encephalitis as Treatment-Responsive Cause of Rapidly Progressive Dementia: A Multicenter Prospective Cohort Study.Neurology · 2026Observational
- Longitudinal CSF and Serum Biomarker Dynamics in Tofersen-TreatedInternational journal of molecular sciences · 2026Article
- Prognostic Value of CSF Total Tau Protein in Patients with Familial and Sporadic Creutzfeldt-Jakob Disease.Dementia and geriatric cognitive disorders · 2026Article
- Multimodal Biomarker Characterization of the ALS/FTD Spectrum: A Real-World Clinical Dataset Analysis.International journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
25 authors.
Carolina SoaresDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-2338-4495
Bruna BellaverDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Pamela C L FerreiraDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-2134-9829
Guilherme PovalaDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Cristiano Schaffer AguzzoliDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-7378-3830
João Pedro Ferrari-SouzaDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-2183-1551
Hussein ZalzaleDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Firoza Z LussierDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Francieli RohdenDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Sarah AbbasDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Guilherme Bauer-NegriniDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Douglas Teixeira LeffaDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-4890-8451
Andréa Lessa BenedetDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Rebecca LanghoughWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Tobey J BetthauserWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.ORCID http://orcid.org/0000-0001-8856-1352
Bradley T ChristianWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.ORCID http://orcid.org/0000-0002-9653-559X
Rachael E WilsonWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Dana L TudorascuDepartment of Psychiatry, School of Medicine, 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, Montreal, QC, Canada.ORCID http://orcid.org/0000-0001-9116-1376
Thomas K KarikariDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-1422-4358
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.ORCID http://orcid.org/0000-0003-3930-4354
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.ORCID http://orcid.org/0000-0002-1890-4193
Eduardo R ZimmerGraduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.ORCID http://orcid.org/0000-0002-5349-0053
Sterling C JohnsonWisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.ORCID http://orcid.org/0000-0002-8501-545X
Tharick A PascoalDepartment of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. pascoalt@upmc.edu.ORCID http://orcid.org/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 HOWARD J AIZENSTEIN, Ann D. Cohen · 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
$35.6MWisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin · 2019 to 2026
$34.5MResearch Education ComponentP30AG066468 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI C. Elizabeth Shaaban · 2020 to 2026
$29.4MThe 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
$18.8MMild Cognitive Impairment: A Prospective Community StudyR37AG023651 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Carmen Andreescu, MARY GANGULI · 2021 to 2026
$18.2MPlasma 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
$14.5MThe RAW Brain - The Effect of Rumination, Anxiety and Worry on Aging and Dementia RiskR01MH108509 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Carmen Andreescu · 2016 to 2026
$10.6MPredictors of Altered CNS Structure, Function, and Connectomics in the Elderly using a Health Disparities FrameworkR01AG072641 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ann D. Cohen · 2022 to 2026
$9.6MAlzheimer Diagnosis in older Adults with Chronic Conditions ADACC NetworkU24AG082930 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Nicole R. Fowler, Thomas K Karikari · 2023 to 2026
$7.3MAlzheimerfonden AF-939721Alzheimerfonden AF-968270Alzheimer's Association 24AACSF-1200375Alzheimer's Association 24AARFD-1243899Alzheimer's Association AACSF-20-648075Alzheimer's Association AARFD-22-923814Alzheimer's Association AARFD-22-974627Alzheimer's Association AARFD-23-1150249Alzheimer's Association AARGD-21-850670Alzheimer's Association ADSF-21-831376-CAlzheimer's Association ADSF-21-831377-CAlzheimer's Association ADSF-21-831381-CAlzheimer's Drug Discovery Foundation (ADDF) 201809-2016862Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brazilian Federal Agency for the Support and Evaluation of Graduate Education) 88887.696202/2022-00Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brazilian Federal Agency for the Support and Evaluation of Graduate Education) 88887.951210/2024-00Fonds de Recherche du Québec - Santé (Fonds de la recherche en sante du Quebec) 2020-VICO-279314Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Research Support Foundation of the State of Rio Grande do Sul) 21/2551-0000673-0Hjärnfonden (Swedish Brain Foundation) ALZ2022-0006Hjärnfonden (Swedish Brain Foundation) FO2017-0243Ministry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development) 141357/2020-7Ministry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development) 200691/2021-0National Academy of Neuropsychology (National Academy of Neuropsychology, Inc.) ALZ-NAN-22-928381NIA NIH HHS P01 AG025204NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066468NIA NIH HHS R01 AG021155NIA NIH HHS R01 AG025516NIA NIH HHS R01 AG027161NIA NIH HHS R01 AG072641NIA NIH HHS R01 AG073267NIA NIH HHS R01 AG075336NIA NIH HHS R01 AG083156NIA NIH HHS R01 AG083874NIA NIH HHS R37 AG023651NIA NIH HHS RF1 AG027161NIA NIH HHS RF1 AG077474NIA NIH HHS U24 AG082930NIMH NIH HHS R01 MH108509NINDS NIH HHS U01 NS131740NINDS NIH HHS U01 NS141777U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) U01 NS131740, U01 NS141777U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) 5R01AG073267U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) 5R01AG075336U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG027161, AG021155 and AG062715U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) P01 AG025204-17Weston Brain Institute 8400707Weston Brain Institute 8401103Weston Brain Institute 8401154
Abstract
Cerebrospinal fluid (CSF) total tau (t-tau) is considered a biomarker of neuronal degeneration alongside brain atrophy and fluid neurofilament light chain protein (NfL) in biomarker models of Alzheimer's disease (AD). However, previous studies show that CSF t-tau correlates strongly with synaptic dysfunction/degeneration biomarkers like neurogranin (Ng) and synaptosomal-associated protein 25 (SNAP25). Here, we compare the association between CSF t-tau and synaptic degeneration and axonal/neuronal degeneration biomarkers in cognitively unimpaired and impaired groups from two independent cohorts. We observe a stronger correlation between CSF t-tau and synaptic biomarkers than neurodegeneration biomarkers in both groups. Synaptic biomarkers explain a greater proportion of variance in CSF t-tau levels compared to neurodegeneration biomarkers. Notably, CSF t-tau levels are elevated in individuals with abnormalities only in synaptic biomarkers, but not in individuals with abnormalities only in neurodegeneration biomarkers. Our findings suggest that CSF t-tau is a closer proxy for synaptic degeneration than for axonal/neuronal degeneration.
Indexed as
Alzheimer DiseaseNerve DegenerationSynapsestau ProteinsAgedAged, 80 and overBiomarkersCohort StudiesFemaleHumansMaleMiddle AgedNeurofilament ProteinsNeurograninSynaptosomal-Associated Protein 25BiomarkersMAPT protein, humanneurofilament protein LNeurofilament ProteinsNeurograninSNAP25 protein, humanSynaptosomal-Associated Protein 25tau Proteins
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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.