Evidence map›Paper›PMID 41959774›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Abnormalities in core AD biomarkers precede inflammatory and glial markers in CSF in Autosomal Dominant Alzheimer's Disease.

Wenjing Lin, Aleksandra Beric, Julie K Wisch, Bryce Baker, Gina Jerome, Matthew Minton, Sam Preminger, Jennifer Stauber, Suzanne E Schindler, Jeffrey L Dage and 34 more

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

44 authors.

Wenjing LinDepartment of Psychiatry, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA. NeuroGenomics and Informatics Center, Washington University in Saint Louis School of Medicine, St. Louis, MO 63108, USA.
Aleksandra BericDepartment of Psychiatry, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA. NeuroGenomics and Informatics Center, Washington University in Saint Louis School of Medicine, St. Louis, MO 63108, USA.ORCID 0000-0002-9351-585X
Julie K WischDepartment of Neurology, Washington University in Saint Louis School of Medicine, St. Louis, MO, 63110, USA.ORCID 0000-0003-3624-2784
Bryce BakerDepartment of Psychiatry, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.
Gina JeromeDepartment of Psychiatry, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.
Matthew MintonDepartment of Psychiatry, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.
Sam PremingerDepartment of Psychiatry, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.
Jennifer StauberDepartment of Psychiatry, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.
Suzanne E SchindlerDepartment of Neurology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.
Jeffrey L DageDepartment of Neurology, Indiana University, Indianapolis, IN 46202-3082, USA.ORCID 0000-0002-2192-1699
Ricardo AllegriInstituto Neurológico Fleni, Buenos Aires, Argentina.ORCID 0000-0001-7166-1234
David AguillonGrupo de Neurociencias de Antioquia (GNA), Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.ORCID 0000-0003-2283-536X
Tammie BenzingerDepartment of Radiology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0002-8114-0552
Jasmeer ChhatwalMassachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School.ORCID 0000-0002-7792-1698
Alisha DanielsDepartment of Neurology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.ORCID 0009-0001-1464-6465
Gregory S DayDepartment of Neurology, Mayo Clinic in Florida; Jacksonville, FL, USA.ORCID 0000-0001-5133-5538
Emma DevenneyNeuroscience Research Australia, Sydney NSW 2031 Australia; School of Clinical Medicine, University of New South Wales, Sydney NSW 2052 Australia.
Nick C FoxDementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom; UK Dementia Research Institute at UCL, London, United Kingdom.
Alison GoateDepartment of Genetics & Genomic Sciences, Icahn Genomics Institute; Icahn School of Medicine at Mount Sinai, New York, NY.ORCID 0000-0002-0576-2472
Brian A GordonDepartment of Radiology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0003-2109-2955
Nicolas R BarthélemyDepartment of Neurology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Jason HassenstabDepartment of Neurology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.
Edward HueyDepartment of Psychiatry and Human Behavior, Alpert Medical School, Brown University.ORCID 0000-0002-8295-5884
Takeshi IkeuchiBrain Research Institute, Niigata University, Niigata 9518585, Japan.ORCID 0000-0001-8828-8085
Suman JayadevDepartment of Neurology, University of Washington.
Mathias JuckerGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.ORCID 0000-0001-9045-1072
Takanobu IshiguroBrain Research Institute, Niigata University.ORCID 0000-0002-8205-4912
Jae-Hong LeeDepartment of Neurology, Asan Medical Center, Seoul, Republic of Korea.
Allan I LeveyDepartment of Neurology, Emory University, Atlanta, GA 30329.
Johannes LevinGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
John C MorrisWashington University in St. Louis, Department of Neurology and the Knight Alzheimer Disease Research Center.
Richard J PerrinDepartment of Pathology and Immunology, Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
Alan RentonRonald M. Loeb Center for Alzheimer's Disease, Dept of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jee Hoon RohDepartment of Neurology, Korea University Anam Hospital, Seoul 02841, Republic of Korea; Department of Physiology, Korea University College of Medicine, Seoul 02841, Republic of Korea; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea.ORCID 0000-0002-3243-0529
Chengjie XiongDepartment of Statistics, Washington University in St. Louis, School of Medicine.
Randall J BatemanDepartment of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.ORCID 0000-0002-7729-1702
Beau M AncesDepartment of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-0276-2899
Celeste M KarchDepartment of Psychiatry, Washington University in St Louis.ORCID 0000-0002-6854-5547
Charlene Supnet-BellDepartment of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.ORCID 0000-0001-6917-770X
Jorge Llibre-GuerraDepartment of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.ORCID 0000-0002-2137-7750
Eric McDadeDepartment of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
Dominantly Inherited Alzheimer Network
Laura IbanezDepartment of Psychiatry, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA. Hope Center for Neurological Disorders, Washington University in Saint Louis School of Medicine, St. Louis, MO 63108, USA. NeuroGenomics and Informatics Center, Washington University in Saint Louis School of Medicine, St. Louis, MO 63108, USA. Department of Neurology, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.ORCID 0000-0003-2381-7059

Funding

Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
Imaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9M
DIAN-TU Next Generation Prevention Trial - Data Request Management SupplementR01AG053267 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2017 to 2023
$34.9M
Research Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI Susan Lynn Stark · 2020 to 2026
$28.7M
Investigations of Dementia in Parkinson DiseaseRF1NS075321 · NINDS · WASHINGTON UNIVERSITY · PI CAMPBELL, MEGHAN C, PERLMUTTER, JOEL SYNES · 2023 to 2023
$2.3M
Plasma Cell-Free RNA as Non-invasive Biomarker for NeurodegenerationR00AG062723 · NIA · WASHINGTON UNIVERSITY · PI IBANEZ, LAURA · 2022 to 2024
$729k
Plasma Cell-Free RNA as Non-invasive Biomarker for NeurodegenerationK99AG062723 · NIA · WASHINGTON UNIVERSITY · PI IBANEZ, LAURA · 2020 to 2021
$250k
NIA NIH HHS K99 AG062723NIA NIH HHS P01 AG003991NIA NIH HHS P30 AG066444NIA NIH HHS R00 AG062723NIA NIH HHS R01 AG053267NIA NIH HHS U19 AG032438NINDS NIH HHS RF1 NS075321
6 · The paper itself

Abstract

backgroundIncreasing evidence suggests that accurate prediction of Alzheimer's disease (AD) symptom onset requires more than amyloid- and tau-centric biomarkers such as cerebrospinal fluid (CSF) Aβ42/40, total tau and p-tau181 and plasma p-tau217. Autosomal dominant AD (ADAD), caused by pathogenic

methodsWe measured 972 CSF samples corresponding to 484 participants of the Dominantly Inherited Alzheimer Disease Network (DIAN) using the NULISASeq 120 CNS Disease Panel. We first benchmarked the technology against gold-standard measurements followed by the identification of proteins that were differentially abundant in relation to mutation status and symptomatology. Next, we determined the chronological emergence of protein changes in relation to the estimated years to onset (EYO). Finally, we assessed whether specific protein measures improved the prediction of EYO in the ADAD.

findingsNULISA measurements were comparable to those previously published. We demonstrated that known early alterations in CSF amyloid and tau were followed by inflammatory and neurodegenerative responses suggesting that clinical manifestation of AD happens before the inflammatory processes is fully developed. Finally, we found a multi-protein composite approach for predicting EYO that outperformed single biomarker values.

interpretationOur results suggest that the main CSF proteomic landscape changes in ADAD are due to the presence of a pathogenic mutation and occur prior to symptom onset. Improved performance of multi-protein composite to predict EYO compared to single biomarker values highlights the added value of multiplex proteomic signatures for biomarker panel development.

Identifiers

PMID41959774
PMCPMC13060398

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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.