Objective: The scope of this work was to characterise the B-cell receptor repertoire of patients with Parkinson’s disease with dementia (PDD), cognitively resilient (PDR) and healthy controls (HC) in a diverse population.
Background: PDD is one of the most feared aspects of Parkinson’s disease (PD)1. There is a lack of biomarkers for incipient PDD. B-cell repertoire analysis could be a PDD biomarker. B-cell repertoires show more activated B-cells in patients with PD than controls, suggesting higher immune activation2. However, the role of B-cells in PD progression, including dementia, is not known.
Method: The East London Parkinson Disease project is a platform study aiming to understand the manifestations and determinants of PD in a diverse population3. Patients with PD were recruited from the Royal London Hospital. For PDD diagnosis, a multidisciplinary team meeting was established to discuss cases and find consensus. PDR was defined as cognitively normal after 8 years of PD symptoms. B-cell receptor repertoires were generated using both single-cell and bulk transcriptomics. Cells isolated from venous blood were used as the input to build subject specific B-cell receptor libraries in both cases. Mutation counts, class-switching proportions, and Shannon index in B-cell receptor repertoires were used to investigate immune activation. Data was analysed with Mann-Whitney U tests, and Chi-squared in Python v3.10.5, with Bonferroni correction.
Results: We collected 85 blood samples from 32 PDD, 37 PDR, and 16 HC. PDD patients were older than PDR and HCs (76±7 years vs 65±17, p<0.001, and 59±14, p<0.001, respectively). B-cell receptor sequencing was undertaken in 28 samples for single-cell, and in 24 samples for bulk. Mutation counts were higher in PDD (0.002) compared to PDR (0.0004) and HC (0.0003), p<0.001. Class-switched B-cells were more abundant in PDD compared to PDR in single-cell data (p=0.002) and HC in bulk data (p=0.013). A lower Shannon index was detected in bulk data in PDD (16.9) compared to PDR (19) and HC (20.5), p<0.001.
Conclusion: Our study suggests that PDD patients have signs of higher immune activation compared to PDR and HC in the diverse East London PD population. Further work is needed for understanding the role of B-cells in PDD progression.
References: 1. Aarsland, D. et al. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers 7, 47 (2021).
2. Wang, P. et al. Global Characterization of Peripheral B Cells in Parkinson’s Disease by Single-Cell RNA and BCR Sequencing. Front Immunol 13, 814239 (2022).
3. Zirra, A. et al. The East London Parkinson′s Disease Project – A case-control study in a diverse population. medRxiv (2024) doi:10.1101/2024.11.24.24317730.
To cite this abstract in AMA style:
A. Zirra, KC. Dey, E. Camboe, E. Bhadra, B. Huxford, R. Laban, N. Donkor, F. Nice, S. Valle Thomas, A. Gaspariunas, L. Mitchell, DA. Gallagher, C. Budu, C. Simonet, T. Boyle, AJ. Lees, D. Yadin, J. Dias, O. Cavlan, CR. Marshall, MT. Perinan, AJ. Noyce. The East London Parkinson Disease Project: Higher Immune Activation found in Patients with Parkinson’s Disease Dementia from a Diverse Population [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/the-east-london-parkinson-disease-project-higher-immune-activation-found-in-patients-with-parkinsons-disease-dementia-from-a-diverse-population/. Accessed November 20, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-east-london-parkinson-disease-project-higher-immune-activation-found-in-patients-with-parkinsons-disease-dementia-from-a-diverse-population/