{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:13:50Z","timestamp":1788783230311,"version":"build-2803163510"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Corticobasal degeneration (CBD) is a late onset progressive neurodegenerative condition of the 4-repeat-tauopathy-type, classically presenting with asymmetrical rigidity, dystonia and myoclonus. In the most recent diagnostic criteria, Armstrong and colleagues (2013) described four clinical phenotypes associated with this pathology, including corticobasal syndrome (CBS), through a large retrospective analysis of published cases and confirmed brain bank cases of CBD. However, predicting CBD pathology remains challenging.<\/jats:p>\n                  <jats:p>With the advent of disease-modifying therapies, it has become particularly important to distinguish Alzheimer\u2019s disease pathology from other underlying pathologies. We therefore combined two prospectively recruited cohorts of patients with CBS and analysed their key demographic, clinical and biomarker features. We included a separate cohort from UK brain banks who were diagnosed with CBS in life. We divided patients into three groups: CBS-Alzheimer\u2019s (CBS-AD), CBS-non-Alzheimer\u2019s (CBS-non-AD) and CBS-indeterminate (CBS-IDT) based on biomarkers and pathology, comparing clinical features, regional volumetric MRI measures and Nucleic Acid-Linked Immuno-Sandwich Assay with detection by next generation sequencing (NULISAseq) blood protein levels between groups. We performed additional analyses of pathologically verified cases.<\/jats:p>\n                  <jats:p>We included 397 participants, of which 57.7% were female. The mean age at symptom onset was 65.9 years. AD biomarkers and pathology permitted classifying 47 (11.8%) of the cases as CBS-AD, 134 (33.8%) as CBS-non-AD and 216 (54.4%) as CBS-IDT. Patients with CBS-AD had a younger age at onset (61.8 years vs 66.1 years, P\u2009&amp;lt;\u20090.01 and less severe motor deficits (non-significantly lower scores on MDS-UPDRS and PSPRS) and more severe cognitive impairment (non-significantly lower scores on MoCA). Patients with CBS-AD had higher rates of cortical sensory impairment (P\u2009=\u20090.087) and lower rates of limb dystonia (P\u2009&amp;lt;\u20090.01) and falls (P\u2009&amp;lt;\u20090.01) compared to the CBS-non-AD group. Volumetric MRI analysis revealed smaller parietal lobe volumes in CBS-AD (P\u2009=\u20090.01). The most common pathological diagnoses were PSP, CBD and AD. Limb dystonia was more common in people with CBD and PSP pathology (P\u2009=\u20090.077). Falls, impaired verbal fluency and impaired vertical saccades were confirmed as more common in PSP (P\u2009=\u20090.046, P\u2009=\u20090.040, P\u2009=\u20090.012, respectively).<\/jats:p>\n                  <jats:p>In summary, younger onset, less parkinsonism and more cognitive and cortical sensory impairment, along with reduced MRI parietal volumes point to CBS-AD, while limb dystonia, falls and worse verbal fluency relate to CBS-non-AD. Clinical, imaging and blood-biomarkers in can augment the Armstrong criteria in predicting the underlying pathology of corticobasal syndromes.<\/jats:p>","DOI":"10.1093\/brain\/awag257","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:13:49Z","timestamp":1785323629000},"source":"Crossref","is-referenced-by-count":0,"title":["Defining the underlying pathology of corticobasal syndrome using clinical features and biomarkers"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7303-6416","authenticated-orcid":false,"given":"David P","family":"Vaughan","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG ,","place":["UK"]},{"name":"Movement Disorders Centre, UCL Queen Square Institute of Neurology , London, WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marte Theilmann","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG ,","place":["UK"]},{"name":"Movement Disorders Centre, UCL Queen Square Institute of Neurology , London, WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8117-742X","authenticated-orcid":false,"given":"Raquel","family":"Real","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG ,","place":["UK"]},{"name":"Movement Disorders Centre, UCL Queen Square Institute of Neurology , London, WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riona G","family":"Fumi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG ,","place":["UK"]},{"name":"Movement Disorders Centre, UCL Queen Square Institute of Neurology , London, WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5464-5603","authenticated-orcid":false,"given":"Lesley","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG ,","place":["UK"]},{"name":"Movement Disorders Centre, UCL Queen Square Institute of Neurology , London, WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Lux","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London , London, WC1N 3BG 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