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Advances in positron emission tomography (PET) imaging have enabled in vivo visualization of these pathologies, particularly tau and \u03b1-synuclein fibrils, facilitating early diagnosis and differential classification. Tau PET tracers such as 18F-florzolotau have demonstrated robust imaging of both AD-type and 4-repeat tauopathies, including atypical parkinsonian syndromes in FTLD such as progressive supranuclear palsy and corticobasal degeneration. Cryo-electron microscopy has elucidated the molecular interactions underlying tracer binding, highlighting hydrophobic grooves in cross-\u03b2structures as binding components commonly present in multiple tau fibril types. For \u03b1-synucleinopathies, new tracers with a modified cross-\u03b2-binding scaffold, including 18F-SPAL-T-06 and 18F-C05-05, have shown promise in detecting MSA-related pathology and, more recently, midbrain pathology in PD and DLB. However, sensitive detection of pathologies in early PD\/DLB stages remains a challenge. The integration of high-resolution PET technologies and structurally optimized ligands may enable earlier and more accurate detection of protein aggregates, supporting both clinical decision-making and the development of targeted disease-modifying therapies.<\/jats:p>","DOI":"10.3390\/cells14181418","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T14:14:55Z","timestamp":1757513695000},"page":"1418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Imaging of Proteinopathies in the Brains of Parkinsonian Disorders"],"prefix":"10.3390","volume":"14","author":[{"given":"Makoto","family":"Higuchi","sequence":"first","affiliation":[{"name":"Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"},{"name":"Neuroetiology and Diagnostic Science, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/s41582-025-01126-2","article-title":"Advances in PET imaging of protein aggregates associated with neurodegenerative disease","volume":"21","author":"Higuchi","year":"2025","journal-title":"Nat. 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