Journal Article

DZNE-2026-00167

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Biomarker-Based Classification of Corticobasal Syndrome.

Palleis, C. (First author)DZNE* ; Bernhardt, A. M. (First author)DZNE* ; Weidinger, E.DZNE* ; Fietzek, U. M.DZNE* ; Jäck, A.DZNE* ; Katzdobler, S.DZNE* ; Gnoerich, J.Extern* ; Bauer, T. ; Franzmeier, N. ; Perneczky, R.DZNE* ; Tauopathies, G. I. I. f. (Collaboration Author) ; Brendel, M. (Last author)DZNE* ; Levin, J. (Last author)DZNE* ; Höglinger, G. U. (Last author)DZNE*

2026
Wiley New York, NY

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Please use a persistent id in citations: doi:10.1002/mds.70070

Abstract: Corticobasal syndrome (CBS) is a clinically defined syndrome with progressive movement and cortical dysfunction, caused by various underlying pathologies, most commonly tau-predominant pathologies such as progressive supranuclear palsy and corticobasal degeneration, or Alzheimer's disease (AD). Lewy-type α-synucleinopathies (LTS), TDP-43 proteinopathies, and mixed pathologies may also underlie CBS. The clinical impact of these pathologies remains poorly understood.To subclassify CBS patients in vivo using biomarkers for amyloid-β (Aβ), Tau, and α-synuclein (αSyn), and assess the clinical relevance of this stratification.We conducted a prospective cohort study of 50 CBS patients at LMU University Hospital Munich. Biomarker analysis included cerebrospinal fluid (CSF) Aβ42 and Aβ42/40, [18F]flutemetamol Aβ-PET, [18F]PI-2620 tau-PET, and αSyn seed amplification assays in CSF. CSF neurofilament light chain (NfL) served as a marker of neurodegeneration. Patients were stratified into six groups based on biomarker positivity.Tau positivity was found in 90% of CBS cases, Aβ in 28%, and αSyn in 24%. Stratification identified: 52% consistent with tau-predominant pathology, 18% with AD, 10% with AD+LTS, 10% with tau-predominant+LTS, 4% with isolated LTS, and 6% unclassified. αSyn positivity was more frequent in AD-CBS (36%) than in tau-predominant-CBS (16%). Aβ-positive cases showed greater cognitive impairment; Tau positivity correlated with worse motor symptoms; αSyn-positive patients had milder motor symptoms, slower progression, and lower NfL levels.CBS is molecularly heterogeneous. Biomarker-based classification may enhance diagnostic precision and support personalized therapeutic strategies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Female (MeSH) ; Aged (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; Middle Aged (MeSH) ; tau Proteins: cerebrospinal fluid (MeSH) ; Positron-Emission Tomography (MeSH) ; alpha-Synuclein: cerebrospinal fluid (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; Prospective Studies (MeSH) ; Corticobasal Degeneration: classification (MeSH) ; Corticobasal Degeneration: cerebrospinal fluid (MeSH) ; Corticobasal Degeneration: diagnostic imaging (MeSH) ; Peptide Fragments: cerebrospinal fluid (MeSH) ; Aged, 80 and over (MeSH) ; proteinopathies ; tau‐PET ; α‐synuclein seed amplification assay ; β‐amyloid ; Biomarkers ; Amyloid beta-Peptides ; tau Proteins ; alpha-Synuclein ; Peptide Fragments ; amyloid beta-protein (1-42)

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))
2. Clinical Neurodegeneration (AG Levin)
3. Molecular Neurodegeneration (AG Haass)
4. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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