A Biomarker-Based Classification of Corticobasal Syndrome.

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2025-10-06 DOI:10.1002/mds.70070

Carla Palleis,Alexander Maximilian Bernhardt,Endy Weidinger,Urban M Fietzek,Alexander Jäck,Sabrina Katzdobler,Johannes Gnörich,Theresa Bauer,Nicolai Franzmeier,Robert Perneczky, ,Matthias Brendel,Johannes Levin,Günter U Höglinger

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引用次数: 0

Abstract

BACKGROUND 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. OBJECTIVES 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

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皮质基底综合征的生物标志物分类。

背景：皮质基底综合征（CBS）是一种临床定义的进行性运动和皮质功能障碍综合征，由多种潜在病理引起，最常见的是tau显性病理，如进行性核上性麻痹和皮质基底变性，或阿尔茨海默病（AD）。路易型α-突触核蛋白病（LTS）、TDP-43蛋白病和混合病理也可能是CBS的基础。这些病理的临床影响仍然知之甚少。目的利用淀粉样蛋白-β (Aβ)、Tau和α-突触核蛋白（αSyn）的生物标志物对CBS患者进行体内亚分类，并评估这种分层的临床相关性。方法：我们对慕尼黑LMU大学医院的50例CBS患者进行了前瞻性队列研究。生物标志物分析包括脑脊液（CSF） Aβ42和Aβ42/40， [18F]氟替他莫Aβ-PET， [18F]PI-2620 tau-PET，脑脊液αSyn种子扩增检测。脑脊液神经丝轻链（NfL）作为神经退行性变的标志。根据生物标志物阳性程度将患者分为六组。结果stau阳性占CBS病例的90%，α β阳性占28%，αSyn阳性占24%。鉴定的分层：52%符合tau显性病理，18%为AD， 10%为AD+LTS， 10%为tau显性+LTS， 4%为孤立性LTS， 6%未分类。αSyn阳性在AD-CBS组（36%）高于tau- dominant- cbs组（16%）。a β阳性患者表现出较大的认知障碍；Tau蛋白阳性与运动症状加重相关；α syn阳性患者运动症状较轻，进展较慢，NfL水平较低。结论scbs具有分子非均质性。基于生物标志物的分类可以提高诊断的准确性，支持个性化的治疗策略。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.