Atypical Parkinsonian Disorders: Where Diagnosis, Imaging, and Disease-Modifying Treatment Stand Today — Across PSP, MSA, CBS, and DLB

This research brief, compiled in September 2026, highlights the latest advancements in Atypical Parkinsonian Disorders (APD)—a group of rare, rapidly progressive neurodegenerative syndromes that mimic idiopathic Parkinson's disease in their initial motor features but diverge sharply in underlying pathology and disease course. The brief focuses on four key neurodegenerative APDs: progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). It spans six core sections detailing the current landscape of the field: Diagnosis: Moving from purely descriptive frameworks to structured, biology-driven criteria backed by diagnostic algorithms and white matter integrity analysis. Molecular Imaging: Highlighting the breakthrough of α-synuclein PET tracers (such as [18F]ACI-12589 and SY08) that allow direct visualization of pathology in living brains. PSP Therapies: Tracking disease-modifying treatments targeting tau pathology, including antisense oligonucleotides, Phase 3 trials, and large-scale clinical trial platforms. MSA Therapies: Reviewing direct α-synuclein targets like the Amlenetug Phase 3 trial, oral small molecules, and iron dysregulation approaches. Care Gaps: Addressing underserved areas such as mixed dysarthrias, motor speech disorders, and the necessity of coordinated multidisciplinary care visits. Outlook: Summarizing future hurdles, including biomarker validation, regulatory qualification, and the ongoing shift toward combination therapies.