A recent study by Luca Magistrelli et al., published in the journal BrainBehaviorand Immunity shows that patients with Parkinson’s disease (PD) and cognitive decline exhibit a preferential pro-inflammatory immune phenotype and a dysregulation in the CD4+ T regulatory compartment.
Parkinson’s disease represents the second most common chronic neurodegenerative disease, and it is caused by the loss of dopaminergic neurons in the pars compacta of the substantia nigra. The mechanisms leading to this neuronal loss are not yet fully understood but it is now clear that they may be the result of multifactorial causes.
In the last few years, several lines of research have highlighted the importance of the peripheral immune system in the pathophysiology of PD, but how it may infleunce the motor and non-motor symptoms has not yet been clearly established.
In this study, the authors analyze whether in PD patients peripheral CD4+ T cells may be related to cognitive decline, a frequent complication of PD. 43 PD patients were enrolled and 14 of them were drug naive. Cognitive assessment was performed using the Addenbrooke test, which allows a brief overview on different cognitive functions (memory, attention/orientation, fluency, visuospatial and language).
When considering the whole population, patients with worse cognitive scores presented a higher number of total lymphocytes and displayed a preferential pro-inflammatory immune phenotype characterized by an increase of T helper (Th) 1 cells.
Interestingly, when considering the drug naive patients, significant differences in the regulatory T cells (Tregs) populations were detected. Particularly, patients with a cognitive decline presented an increased active Treg and reduced naive Treg. These differences in drug naive patients may represent an early signature of cognitive decline, or alternatively subsequent anti-parkinsonian therapy may affect this specific profile.
The study also detected a negative correlation between total lymphocytes and Addenbrooke memory/attention subitem, and between total number of central memory CD4+ T lymphocytes and Addenbrooke fluency score.
These data reinforce the concept that peripheral immunity is involved in the pathophysiology of cognitive decline in PD. The dysregulation of the T regulatory compartment in particular may impair the anti-inflammatory functions of these cells, thus contributing to the perpetuation of an inflamed central environment resulting in worsening of neurodegeneration.
Finally, this study strengthens the notion that the peripheral immune system represents a suitable therapeutic target also in the early stages of PD, in order to possibly modify the clinical course.
Luca Magistrelli, MD, PhD – Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy, and PhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, Varese, Italy
Cover Image: A model developed at MIT predicts the cognitive decline of patients at risk for Alzheimer’s disease by forecasting their cognition test scores up to two years in the future, which could help zero in on the right patients to select for clinical trials. Image credit: Christine Daniloff, MIT; source: https://news.mit.edu/2019/model-predicts-alzheimers-decline-0802