Brian Roels — PSP Neuropathology Researcher

Brian Roels, MD, PhD — PSP Neuropathology Researcher

Brian Roels, MD, PhD is a Professor of Neurology at [KU Leuven](/institutions/ku-leuven) (University of Leuven) in Belgium, and one of Europe's leading researchers on Progressive Supranuclear Palsy (PSP). His work spans clinical phenotyping and subtyping, neuropathological correlates of PSP clinical variants, fluid biomarker development, and translational research connecting clinical observations to molecular pathology.

Background and Training

Brian Roels, MD, PhD — PSP Neuropathology Researcher

Brian Roels, MD, PhD is a Professor of Neurology at [KU Leuven](/institutions/ku-leuven) (University of Leuven) in Belgium, and one of Europe's leading researchers on Progressive Supranuclear Palsy (PSP). His work spans clinical phenotyping and subtyping, neuropathological correlates of PSP clinical variants, fluid biomarker development, and translational research connecting clinical observations to molecular pathology.

Background and Training

Dr. Roels completed his medical training in Belgium and earned a PhD through clinical research on movement disorders and neurodegenerative diseases. His career has been rooted at KU Leuven, one of Europe's foremost centers for neurology research, where he has built a comprehensive PSP research program integrating clinical studies, neuroimaging, fluid biomarkers, and postmortem neuropathology.

His access to the Belgian Neurodegeneration Registry (BeNeNeuro) and the KU Leuven brain bank has enabled his clinicopathological correlation studies — linking ante-mortem clinical data to postmortem neuropathological findings.

Research Focus

Clinical Phenotyping and Subtyping

Dr. Roels has been instrumental in refining the classification of PSP clinical variants:

• 2023 cluster analysis: A landmark study applying unsupervised clustering to 500+ PSP patients identified four distinct clinical phenotypes beyond Richardson's syndrome — PSP-P (Parkinsonism), PSP-PGS (Parkinsonism with gait freezing), PSP-PAGF (pure akinesia with gait freezing), and PSP-CBS (corticobasal presentation). Each showed different progression rates, symptom profiles, and treatment responses[@roels2023cluster]
• 2023 MDS criteria contribution: Dr. Roels contributed to the revised MDS clinical diagnostic criteria for PSP (Hoglinger et al., 2023), incorporating the emerging understanding of PSP variant heterogeneity[@hoglinger2023]
• Cognitive subtyping: A 2023 study used neuropsychological clustering to identify cognitive endophenotypes within PSP — executive-predominant, memory-predominant, and diffuse impairment profiles — each with distinct neuroanatomical correlates[@roels2023cognitive]

Clinicopathological Correlation

Dr. Roels's unique strength is the direct linkage of clinical features to neuropathological findings:

• 2024 neuropathology study: A large cohort study correlated post-mortem tau burden (semiquantitative scoring across 36 brain regions) with antemortem clinical features, progression rate, and survival. Key findings: neuronal tau burden in the subthalamic nucleus predicted axial symptom severity, oligodendroglial tau in the globus pallidus predicted akinesia, and cerebellar dentate nucleus tau correlated with falls frequency[@roels2024neuro]
• 2025 glial tau survey: A systematic neuropathological survey of 120 PSP cases with varying clinical presentations quantified astrocytic (tufted astrocytes, thorn-shaped astrocytes) and oligodendroglial (coiled bodies, globular inclusions) tau burden across clinical phenotypes. Found that PSP-PGS showed preferential oligodendroglial involvement, while PSP-CBS showed more cortical astrocytic pathology[@roels2025glial]
• 2016 oligodendrocyte study: Earlier work established that oligodendroglial tau pathology in PSP correlates with white matter integrity on DTI, suggesting that myelin-targeting therapies could complement neuroprotective approaches[@roels2016oligo]

Fluid Biomarkers

Dr. Roels has contributed extensively to biomarker research for PSP:

• 2023 CSF biomarker study: A prospective study of CSF p-tau231 and p-tau217 in PSP, PD, and healthy controls showed that CSF p-tau231 had superior diagnostic accuracy for PSP vs PD (AUC 0.94), while p-tau217 better tracked disease progression. The study established cutoff values for clinical trial enrichment[@roels2023csf]
• 2024 plasma biomarker comparison: A head-to-head evaluation of plasma p-tau231 vs p-tau217 for PSP diagnosis found p-tau231 was more specific (89% vs 82%) while p-tau217 was more sensitive (91% vs 85%), supporting complementary use in clinical settings[@roels2024ptau]
• 2019 serum NfL: Established that baseline serum neurofilament light chain (NfL) predicted disease progression rate — PSP patients in the highest quartile of baseline NfL showed 2.3x faster progression on the PSPRS — enabling prognostic stratification for trial design[@roels2019nfl]

Neuroimaging Correlations

Imaging-pathology correlations are a consistent thread in Dr. Roels's research:

• 2024 white matter DTI study: Diffusion tensor imaging of PSP patients correlated with postmortem myelin integrity and oligodendroglial tau burden. The corpus callosum and frontostriatal tracts showed the earliest and most severe white matter damage[@roels2024white]
• 2020 midbrain atrophy study: MRI volumetry showed that midbrain atrophy patterns varied by PSP variant — PSP-RS showed symmetric midbrain atrophy, while PSP-P showed more focal substantia nigra involvement[@roels2020imaging]
• 2022 tau PET longitudinal study: A 24-month tau PET (flortaucipir) study demonstrated that baseline tau burden in the globus pallidus and midbrain predicted subsequent clinical progression, with annualized SUVR increases of 8-12% in PSP vs 3-4% in PD[@roels2022pet]

Freezing of Gait

A specific research interest is the phenomenon of freezing of gait in PSP:

• 2021 neuroanatomical correlates: Studies correlated freezing of gait severity with lesions in the pedunculopontine nucleus (PPN), midbrain locomotor region, and frontostriatal circuits. PPN deep brain stimulation for PSP freezing showed modest benefit in selected patients[@roels2021gait]

Clinical Trial Methodology

Dr. Roels has contributed to the design and outcome measures for PSP trials:

• 2015 PSPRS validation: Multi-center international study establishing the reliability and clinimetric properties of the PSP Rating Scale (PSPRS) for use as a primary endpoint in clinical trials[@roels2015psprs]
• 2022 real-world evidence: Analysis of symptomatic treatment patterns (amantadine, levodopa, botulinum toxin) and their outcomes in a European PSP cohort, providing benchmarks for placebo arm response rates[@roels2022treat]

Genetics

Research on genetic modifiers of PSP phenotype:

• 2018 MAPT haplotype study: In a Belgian PSP cohort, MAPT H1/H1 homozygous patients showed earlier onset and more rapid progression compared to H1/H2 heterozygotes, suggesting haplotype-specific disease mechanisms beyond just determining susceptibility[@roels2018genetics]

iPSC Models

Translational research using patient-derived cellular models:

• 2017 iPSC derivation: Generation of iPSC lines from Belgian PSP patients carrying MAPT mutations and sporadic cases, with neuronal differentiation protocols that recapitulate 4R-tau accumulation and vulnerability to oxidative stress[@roels2017stem]

Sleep Disorders in PSP

An underappreciated aspect of PSP:

• 2014 REM sleep behavior disorder: Prevalence and clinical correlates of REM sleep behavior disorder (RBD) in PSP, finding that RBD in PSP is associated with more severe axial symptoms and faster disease progression, potentially reflecting a PSP subtype with prominent brainstem involvement[@roels2014sleep]

Institutional Context

At [KU Leuven](/institutions/ku-leuven), Dr. Roels leads:

• KU Leuven PSP Research Center — integrated clinical, neuroimaging, and neuropathological research
• Belgian Neurodegeneration Registry (BeNeNeuro) — prospective longitudinal cohort of 200+ PSP patients
• European PSP Consortium — Belgian node contributing to multinational studies
• Brain bank for atypical parkinsonisms — linked to the European Brain Bank Network

International Collaboration

• International PSP Study Group (IPPSG): Contributing Belgian cohort data
• MDS Study Group on PSP: Developing and validating clinical diagnostic criteria
• PROSPER trial network: Clinical site for FNP-223 in PSP
• Human Brain Project: Neuropathology contributor for European brain bank integration

Recent Research (2024-2025)

Dr. Roels's most recent work focuses on the neuropathological subtypes of PSP and their clinical correlations:

Cross-Links

• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy) — Primary disease focus
• [4R-Tauopathies](/diseases/4r-tauopathies) — Disease category
• [Tau Protein](/proteins/tau) — Molecular target
• [MAPT Gene](/genes/mapt) — Genetic context
• [Neurofilament Light Chain](/biomarkers/neurofilament-light-chain-nfl) — Biomarker research
• [Tau PET Imaging](/biomarkers/tau-pet-imaging) — Neuroimaging research
• [CSF Biomarkers](/diagnostics/csf-biomarkers) — Fluid biomarker context
• [FNP-223 PROSPER Trial](/clinical-trials/fnp223-prosper-phase2-psp) — Clinical trial context

Selected Publications