Luca Magistrelli1, Elisa Storelli2, Emanuela Rasini2, Elena Contaldi3, Cristoforo Comi4, Marco Cosentino5, Franca Marino5. 1. Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy; PhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, Varese, Italy. Electronic address: luca.magistrelli@maggioreosp.novara.it. 2. Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy. 3. Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy; PhD Program in Medical Sciences and Biotechnology, University of Piemonte Orientale, Novara, Italy. 4. Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy; Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy. 5. Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy; Center for Research in Neuroscience, University of Insubria, Varese, Italy.
Abstract
INTRODUCTION: Parkinson's disease (PD) is characterized by loss of dopaminergic neurons. Neuroinflammation may represent an important factor in the pathophysiology of PD and recent findings indicate that PD patients present a pro-inflammatory peripheral profile of CD4+ T lymphocytes, which may correlate with motor disability. However, no data are currently available on the relationship between CD4+ T lymphocytes and cognitive function in PD. The aim of our study is to evaluate the relationship between cognitive profile and circulating CD4+ T lymphocyte subsets in PD patients. METHODS: PD patients underwent blood withdrawal and CD4+ T lymphocyte subpopulations, including CD4+ T naïve and memory cells, Th1, Th2, Th17, Th1/17 and T regulatory (Treg) cells were evaluated by flow cytometry. Cognitive evaluation was performed using Addenbrooke Cognitive Examination (ACE-R). RESULTS: 43 consecutive PD patients (31 males; age [mean ± SD]: 68.9 ± 8.4 years) were enrolled. 14/43 (32.6%) were drug naïve. Based on the ACE-R score, patients were divided in two groups using defined cutoff values. In comparison to patients with normal cognitive profile, patients with cognitive impairment had a higher number of circulating lymphocytes. Moreover, drug naïve patients with a worse cognitive outcome had a lower number of resting Treg and higher number of activated Treg. Furthermore, we found a correlation between pro-inflammatory peripheral immune phenotype and worse cognitive outcome in the ACE-R total and sub-items scores. CONCLUSIONS: In our cohort of PD patients, cognitive impairment was associated with higher number of circulating lymphocytes, and - at least in drug naïve patients - with dysregulation of the Treg compartment. Further studies are needed to assess whether and to what extent peripheral immunity mechanistically contributes to cognitive decline in PD.
INTRODUCTION:Parkinson's disease (PD) is characterized by loss of dopaminergic neurons. Neuroinflammation may represent an important factor in the pathophysiology of PD and recent findings indicate that PDpatients present a pro-inflammatory peripheral profile of CD4+ T lymphocytes, which may correlate with motor disability. However, no data are currently available on the relationship between CD4+ T lymphocytes and cognitive function in PD. The aim of our study is to evaluate the relationship between cognitive profile and circulating CD4+ T lymphocyte subsets in PDpatients. METHODS:PDpatients underwent blood withdrawal and CD4+ T lymphocyte subpopulations, including CD4+ T naïve and memory cells, Th1, Th2, Th17, Th1/17 and T regulatory (Treg) cells were evaluated by flow cytometry. Cognitive evaluation was performed using Addenbrooke Cognitive Examination (ACE-R). RESULTS: 43 consecutive PDpatients (31 males; age [mean ± SD]: 68.9 ± 8.4 years) were enrolled. 14/43 (32.6%) were drug naïve. Based on the ACE-R score, patients were divided in two groups using defined cutoff values. In comparison to patients with normal cognitive profile, patients with cognitive impairment had a higher number of circulating lymphocytes. Moreover, drug naïve patients with a worse cognitive outcome had a lower number of resting Treg and higher number of activated Treg. Furthermore, we found a correlation between pro-inflammatory peripheral immune phenotype and worse cognitive outcome in the ACE-R total and sub-items scores. CONCLUSIONS: In our cohort of PDpatients, cognitive impairment was associated with higher number of circulating lymphocytes, and - at least in drug naïve patients - with dysregulation of the Treg compartment. Further studies are needed to assess whether and to what extent peripheral immunity mechanistically contributes to cognitive decline in PD.
Authors: Lars Tönges; Carsten Buhmann; Stephan Klebe; Jochen Klucken; Eun Hae Kwon; Thomas Müller; David J Pedrosa; Nils Schröter; Peter Riederer; Paul Lingor Journal: J Neural Transm (Vienna) Date: 2022-04-15 Impact factor: 3.850