Citations 2
Longitudinal Dynamics of Polyglutamine‐Expanded ATXN3 in Biofluids of Spinocerebellar Ataxia Type 3
Bartfield, Jordan, Milanowski, L, Jansen‐West, Karen , Al‐Shaikh, Rana Hanna , Chmiela, Tomasz , Dunmore, Judith A. , Gorcenco, Sorina , Puschman, Andreas, Lemos, João, Januario, C, Ledoux, Mark S., Onodera, O, Aiba, I, Pfeiffer, Ronald F., Paulson, Henry, McLoughlin, Hayley S., Teive, Helio A.G., Soto-Piña, Alexandra E., Uitti, Ryan J., Strongosky, Audrey, Petrucelli, L, Paulson, Henry L. , Milanowski, Łukasz , Dunmore, Judith A , Gorcenco, Sorina , Friedman, Joseph H. , Sławek, Jarosław , Wszolek, Z.K. , Chmiela, Tomasz , Paulson, Henry L , Milanowski, Łukasz M , Gendron, Tania F. , Lemos, João , Januário, Cristina , Onodera, Osamu , Aiba, Ikuko , Pfeiffer, Ronald F. , McLoughlin, Hayley S. , Dulski, Jarosław , Sławek, Jarosław , Teive, Hélio Afonso Ghizoni , Soto‐Piña, Alexandra Estela , Uitti, Ryan J. , Strongosky, Audrey , Prudencio, Mercedes , Wszołek, Zbigniew K.
Movement Disorders | July 1, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Background Spinocerebellar ataxia type 3 (SCA3), the most common autosomal dominant ataxia, is driven by the accumulation of polyglutamine‐expanded (polyQ) ATXN3 proteins. While promising as biomarkers, their longitudinal trajectories across multiple biofluids remain poorly defined. Objectives To quantify polyQ ATXN3 levels in cerebrospinal fluid (CSF), plasma, and urine within a comprehensive cohort, utilizing serial measurements to map protein dynamics. Methods We employed a validated immunoassay to quantify polyQ ATXN3 in 97 symptomatic and 13 presymptomatic SCA3 patients, correlating levels with clinical features, ancestry, disease status, and longitudinal progression. Results Asian participants exhibited lower plasma but elevated urinary polyQ ATXN3 levels relative to other ancestries. While CSF levels were higher in symptomatic patients at baseline, they showed a significant longitudinal decline. Conclusions PolyQ ATXN3 is a viable multi‐biofluid biomarker. Declining CSF levels likely reflect neurodegeneration, supporting its role in tracking progression and emphasizing the need for ancestry‐based adjustment in trials. © 2026 International Parkinson and Movement Disorder Society.
Progressive Supranuclear Palsy—A Global Review
Kukkle, Prashanth Lingappa , Neupane, Rosy, Wills, Anne‐Marie , Dopper, Elise G.P. , Kovács, Gábor G. , Höglinger, Günter U. , Aiba, Ikuko , Litvan, Irene , Whitwell, Jennifer L. , Whitwell, Jennifer L. , Okeng’o, Kigocha , Forrest, Shelley L. , Lorenzl, Stefan , Compta, Yaroslau , Group, MDS‐PSP Study, Pantelyat, Alex , Wills, Anne-Marie A , Jabbari, Ed , Dopper, Elise G P , Kovacs, Gabor G , Höglinger, Günter U , Litvan, Irene , Ganguly, Jacky , Whitwell, Jennifer L , Whitwell, Jennifer , Sakakibara, Ryuji , Zewde, Yared Zenebe , Morris, Huw R , Pantelyat, Alexander , Sakakibara, Ryuji , Morris, Huw R. , Group, MDS‐PSP Study
Movement Disorders Clinical Practice | September 3, 2025 | Volume: 13 | Issue: 3 | Pages: 611-622
Abstract Background Progressive Supranuclear Palsy (PSP) is a rare and severe neurodegenerative tauopathy characterized by diverse clinical phenotypes, including Richardson's syndrome (PSP‐RS), PSP‐parkinsonism (PSP‐P), PSP‐progressive gait freezing (PSP‐PGF), and PSP‐corticobasal syndrome (PSP‐CBS). Significant geographic variation exists in prevalence, clinical presentations, and prognosis. Objectives This global review aims to systematically evaluate the epidemiological variation, clinical phenotypes, diagnostic practices, and management strategies for PSP, focusing on regional disparities and identifying influencing genetic and environmental factors. Methodology A comprehensive literature search following PRISMA guidelines was conducted, analyzing studies reporting PSP epidemiology, phenotypes, diagnostic criteria, risk factors, treatments, and prognoses. Data were categorized into epidemiology, risk factors, clinical presentations, diagnosis, treatment accessibility, and outcomes, considering geographic variation. Results Global PSP prevalence ranges between 5–6.4 per 100,000, influenced by diagnostic criteria and healthcare infrastructure. Clinical manifestations commonly include supranuclear gaze palsy, frequent falls, cognitive impairment, and motor dysfunction. Prognosis significantly varies with subtype; PSP‐RS shows rapid progression and shorter survival (5–7 years), whereas PSP‐P has a milder clinical course (8–12 years). Regional variations highlight differences in genetic predispositions, notably the MAPT H1 haplotype, environmental risk factors such as dietary neurotoxins and industrial pollutants, and accessibility to comprehensive healthcare services. Diagnostic accuracy has improved with the adoption of MDS‐PSP criteria, facilitating recognition of diverse phenotypes. Conclusions Regional disparities in PSP prevalence, phenotypic presentation, and healthcare accessibility underscore the importance of standardized diagnostic criteria, targeted genetic and environmental studies, and equitable healthcare strategies. Enhanced global collaboration is essential for improving PSP diagnosis, management, and patient outcomes worldwide.