Category: MSA, PSP, CBS: Disease Mechanisms
Objective: Our aim was to examine whether the HLA haplotypes influence the neuroinflammatory response in a cohort of neuropathologically diagnosed PSP cases.
Background: Progressive supranuclear palsy (PSP) is a neurodegenerative 4R tauopathy clinically presenting as atypical parkinsonism or with frontotemporal dementia syndromes. The neuropathology is relatively uniform characterized by neuronal and glial tau pathologies. Some cases show overlap of clinical symptoms and neuropathological features with IgLON5 autoimmune-encephalitis-related tauopathy that is associated with a unique HLA haplotype.
Method: In addition to HLA genotyping, we performed systematic mapping of inflammatory cells and tau cytopathologies and co-pathologies in 45 PSP cases.
Results: Four different haplotype groups were identified in cases with typical PSP neuropathology: i) a single case compatible with the same HLA haplotype found in IgLON5-encephalitis; ii) cases with haplotype that has been described in narcolepsy; iii) a group of patients with a rare haplotype; iv) and haplotypes in the rest of the patients were similar to those found in the general population. Neuropathology examination revealed that the microglial response is significantly higher in patients with the narcolepsy type of haplotype, while T-cells are mostly seen in other the groups and particularly high in the single cases with the haplotype associated with Iglon5 autoimmune disorder.
Conclusion: Our study reveals subgroups of PSP with different HLA haplotypes and neuropathology patterns of inflammatory cell response. This supports the notion that the common neuropathology seen in PSP might be associated with various pathogenic events, some with potential relationships with autoimmune mechanisms.
Partial results of this study were presented at ADPD Conference in Vienna, 4th April, 2025.
To cite this abstract in AMA style:
G. Kovacs, H. Chasiotis, S. Zaheer, J. Wang, J. Li, MC. Tartaglia, S. Fox, A. Lang, S. Forrest. Neuroinflammatory response is determined by HLA genotype in progressive supranuclear palsy [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/neuroinflammatory-response-is-determined-by-hla-genotype-in-progressive-supranuclear-palsy/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroinflammatory-response-is-determined-by-hla-genotype-in-progressive-supranuclear-palsy/