Alzheimer's Disease Co-Pathology and Cognitive Impairment in Amyotrophic Lateral Sclerosis.
Overview
and 10 other authors
Michael Wagner11,21, Frederic Brosseron11, Matthias C. Schmid11,22, Annett Halle11,23, Jochen Herms24,25,26, Anja Schneider11,21, Stefan Teipel2,27, Johannes Prudlo1,2, Manuela Neumann19,28, Andreas Hermann1,2,328 affiliations
- Department of Neurology Rostock University Medical Center Rostock Germany
- German Center for Neurodegenerative Diseases (DZNE) Rostock, Greifswald Germany
- Translational Neurodegeneration Section “Albrecht‐Kossel,” Department of Neurology Rostock University Medical Center Rostock Germany
- German Center for Neurodegenerative Diseases (DZNE) Berlin Germany
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt‐Universität zu Berlin‐Institute of Psychiatry and Psychotherapy Berlin Germany
- Department of Psychiatry and Neurosciences Charité Universitätsmedizin Berlin Berlin Germany
- Charité – Universitätsmedizin Berlin, ECRC Experimental and Clinical Research Center Berlin Germany
- Neuropsychiatry and Laboratory of Molecular Psychiatry, Department of Psychiatry and Psychotherapy Charité ‐ Universitätsmedizin Berlin Berlin Germany
- Department of Psychiatry and Psychotherapy, School of Medicine and Health Technical University of Munich, and German Center for Mental Health (DZPG) Munich Germany
- University of Edinburgh and UK DRI Edinburgh UK
- German Center for Neurodegenerative Diseases (DZNE) Bonn Germany
- Department of Vascular Neurology University Hospital Bonn Bonn Germany
- Department of Neurology University of Bonn Bonn Germany
- German Center for Neurodegenerative Diseases (DZNE) Dresden Germany
- Department of Neurology University Hospital Carl Gustav Carus, Technische Universität Dresden Dresden Germany
- German Center for Neurodegenerative Diseases (DZNE) Magdeburg Germany
- Institute of Cognitive Neurology and Dementia Research, Otto‐von‐Guericke University Magdeburg Germany
- Institute of Cognitive Neuroscience, University College London London UK
- German Center for Neurodegenerative Diseases (DZNE) Tübingen Germany
- Division of Translational Genomics of Neurodegenerative Diseases Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tübingen Tübingen Germany
- Department for Cognitive Disorders and Old Age Psychiatry University Hospital Bonn Bonn Germany
- Institute for Medical Biometry, Informatics and Epidemiology, University Hospital Bonn Bonn Germany
- Department of Neuropathology University of Bonn Bonn Germany
- German Center for Neurodegenerative Diseases (DZNE) Munich Germany
- Munich Cluster for Systems Neurology (SyNergy) Munich Munich Germany
- Department of Neurology University Hospital of Munich, Ludwig‐Maximilians‐Universität (LMU) Munich Munich Germany
- Department of Psychosomatic Medicine Rostock University Medical Center Rostock Germany
- Department of Neuropathology Tübingen University Hospital Tübingen Germany
Abstract
Objectives: Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) share neuropathological features, including tau, amyloid, and TDP‐43 pathology. This study investigated whether AD‐related pathological changes are associated with cognitive impairment ALS.
Methods: Cerebrospinal fluid (CSF total‐tau, phosphorylated‐tau, beta‐amyloid) and plasma biomarkers (TDP‐43; neurofilament light chain [NfL]) were analyzed in 192 individuals with ALS or ALS with frontotemporal dementia (ALS‐FTD) and 100 healthy controls. Cognitive performance was assessed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Group comparisons and regression analyses examined associations between biomarker profiles and cognitive status. Autopsy data were available for a subset of participants.
Results: Compared with healthy controls, patients with ALS – particularly those with cognitive impairment (ALSci) or ALS‐FTD – showed elevated AD‐related biomarkers. Significant differences in beta‐amyloid levels were observed between healthy controls (HCs) and patients with ALSci, but not between controls and cognitively unimpaired patients. CSF p‐tau and total‐tau levels were strongly associated with domain‐specific cognitive performance. In contrast, plasma extracellular vesicle TDP‐43 and NfL showed weak or no association with cognition. In vivo biomarkers alone reliably distinguished cognitive impairment only in ALSci and ALS‐FTD. Postmortem analyses showed no strong association between ABC scores or overall TDP‐43 burden and cognitive state; however, temporal and hippocampal TDP‐43 burden was associated with cognitive dysfunction.
Interpretation: Our findings suggest that tau‐related CSF biomarkers, particularly p‐tau and total‐tau, are associated with cognitive deficits in ALS, indicating that AD‐related pathology might be associated to cognitive decline in ALS. However, postmortem data showed even stronger relation of TDP43 pathology to cognitive deficits in ALS. ANN NEUROL 2026;100:123–138
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 2, 28 September 2026
- Publisher: — → Wiley
- Funding: added Michael J. Fox Foundation for Parkinson's Research; Eli Lilly and Company; Biogen; CHDI Foundation; Teva Pharmaceutical Industries; Verein Deutscher Ingenieure: 13GW0482D; Deutsche Forschungsgemeinschaft; Bundesministerium für Bildung und Forschung; Eisai
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 30 authors, 14 MeSH terms, 44 references.
Cite
This paper
Kasper, E., Lehto, A., Jürs, A., Nordmann, N., Peters, O., Hellmann, J., Priller, J., Spruth, E. J., Petzold, G. C., Voigt, I., Weydt, P., Bernsen, S., Dinter, E., Falkenburger, B., Günther, R., Düzel, E., Glanz, W., Synofzik, M., Beichert, L., . . . Hermann, A. (2026). Alzheimer's Disease Co-Pathology and Cognitive Impairment in Amyotrophic Lateral Sclerosis. Annals of neurology, 100(1), 123-138. https://
BibTeX
@article{kasper2026alzhe
author = {Kasper, Elisabeth and Lehto, Annaliis and Jürs, Alexandra and Nordmann, Nina and Peters, Oliver and Hellmann, Julian and Priller, Josef and Spruth, Eike Jakob and Petzold, Gabor C. and Voigt, Ina and Weydt, Patrick and Bernsen, Sarah and Dinter, Elisabeth and Falkenburger, Björn and Günther, René and Düzel, Emrah and Glanz, Wenzel and Synofzik, Matthis and Beichert, Lukas and Spottke, Annika and Wagner, Michael and Brosseron, Frederic and Schmid, Matthias C. and Halle, Annett and Herms, Jochen and Schneider, Anja and Teipel, Stefan and Prudlo, Johannes and Neumann, Manuela and Hermann, Andreas},
title = {{Alzheimer's Disease Co-Pathology and Cognitive Impairment in Amyotrophic Lateral Sclerosis}},
journal = {Annals of neurology},
year = {2026},
month = may,
volume = {100},
number = {1},
pages = {123--138},
publisher = {Wiley},
issn = {0364-5134},
doi = {10.1002/
url = {https://
pmid = {42112660},
pmcid = {PMC13327596}
}
RIS
TY - JOUR
AU - Kasper, Elisabeth
AU - Lehto, Annaliis
AU - Jürs, Alexandra
AU - Nordmann, Nina
AU - Peters, Oliver
AU - Hellmann, Julian
AU - Priller, Josef
AU - Spruth, Eike Jakob
AU - Petzold, Gabor C.
AU - Voigt, Ina
AU - Weydt, Patrick
AU - Bernsen, Sarah
AU - Dinter, Elisabeth
AU - Falkenburger, Björn
AU - Günther, René
AU - Düzel, Emrah
AU - Glanz, Wenzel
AU - Synofzik, Matthis
AU - Beichert, Lukas
AU - Spottke, Annika
AU - Wagner, Michael
AU - Brosseron, Frederic
AU - Schmid, Matthias C.
AU - Halle, Annett
AU - Herms, Jochen
AU - Schneider, Anja
AU - Teipel, Stefan
AU - Prudlo, Johannes
AU - Neumann, Manuela
AU - Hermann, Andreas
TI - Alzheimer's Disease Co-Pathology and Cognitive Impairment in Amyotrophic Lateral Sclerosis
T2 - Annals of neurology
J2 - Ann Neurol
PY - 2026
DA - 2026/
VL - 100
IS - 1
SP - 123
EP - 138
SN - 0364-5134
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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