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Specific immune status in Parkinson's disease at different ages of onset.

ABSTRACT: Recent evidence suggests that innate and adaptive immunity play a crucial role in Parkinson's disease (PD). However, studies regarding specific immune cell classification in the peripheral blood in PD remain lacking. Therefore, we aimed to explore the different immune status in patients with PD at different ages of onset. We included 22 patients; among them were 10 who had early-onset PD (EOPD) and 12 had late-onset PD (LOPD) and 10 young healthy controls (YHCs) and 8 elder HCs (EHCs). Mass cytometry staining technology was used to perform accurate immunotyping of cell populations in the peripheral blood. Motor symptoms and cognitive function were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) III score and Mini-mental State Examination (MMSE) score, respectively. T test and ANOVA statistical analysis were performed on the frequency of annotated cell population. Linear regression model was used to analyze the correlation between clusters and clinical symptoms. We characterized 60 cell clusters and discovered that the immune signature of PD consists of cluster changes, including decreased effector CD8⁺ T cells, lower cytotoxicity natural killer (NK) cells and increased activated monocytes in PD patients. In summary, we found that CD8⁺ T cells, NK cells, and monocytes were associated with PD. Furthermore, there may be some differences in the immune status of patients with EOPD and LOPD, suggesting differences in the pathogenesis between these groups.

SUBMITTER: Tian J

PROVIDER: S-EPMC8748464 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSeveral previous studies have shown that excessive screen time is associated with an increased prevalence of dementia, Parkinson's disease (PD), and depression. However, the results have been inconsistent. This study aimed to prospectively investigate the association between different types of screen time and brain structure, as well as the incidence of dementia, Parkinson's disease, depression, and their multimorbidity status.MethodsWe included 473,184 participants initially free of dementia, PD, and depression from UK Biobank, as well as 39,652 participants who had magnetic resonance imaging (MRI) data. Screen time exposure variables including TV viewing and computer using were self-reported by participants. Cox proportional hazards regression models were used to estimate the association between different types of screen time and the incidence of dementia, Parkinson's disease, depression, and their multimorbidity status. Multiple linear regression models were used to assess the linear relationship between different types of screen time and MRI biomarkers in a subgroup of participants.ResultsDuring the follow up, 6,096, 3,061, and 23,700 participants first incident cases of dementia, PD, and depression respectively. For moderate versus the lowest computer uses, the adjusted HRs (95% CIs) were 0.68 (0.64, 0.72) for dementia, 0.86 (0.79, 0.93) for PD, 0.85 (0.83, 0.88) for depression, 0.64 (0.55, 0.74) for dementia and depression multimorbidity, and 0.59 (0.47, 0.74) for PD and depression multimorbidity. The multivariable HRs (95% CIs) for the highest versus the lowest group of TV viewing time were 1.28 (1.17, 1.39) for dementia, 1.16 (1.03, 1.29) for PD, 1.35 (1.29, 1.40) for depression, 1.49 (1.21, 1.84) for dementia and depression multimorbidity, and 1.44 (1.05, 1.97) for PD and depression multimorbidity. Moderate computer using time was negatively associated with white matter hyperintensity volume (β = -0.042; 95% CI -0.067, -0.017), and positively associated with hippocampal volume (β = 0.059; 95% CI 0.034, 0.084). Participants with the highest TV viewing time were negatively associated with hippocampal volume (β = -0.067; 95% CI -0.094, -0.041). In isotemporal substitution analyses, substitution of TV viewing or computer using by equal time of different types of PA was associated with a lower risk of all three diseases, with strenuous sports showing the strongest benefit.ConclusionWe found that moderate computer use was associated with a reduced risk of dementia, PD, depression and their multimorbidity status, while increased TV watching was associated with a higher risk of these disease. Notably, different screen time may affect the risk of developing diseases by influencing brain structures. Replacing different types of screen time with daily-life PA or structured exercise is associated with lower dementia, PD, and depression risk.

Project description:While early-onset Parkinson's disease (EOPD) caused by mutations in the parkin gene (PRKN) tends to have a relatively benign course compared to genetically undetermined (GU)-EOPD, the exact underlying mechanisms remain elusive. We aimed to search for the differences between PRKN-EOPD and GU-EOPD by dopamine transporter (DAT) and glucose metabolism positron-emission-tomography (PET) imaging. Twelve patients with PRKN-EOPD and 16 with GU-EOPD who accepted both 11C-2b-carbomethoxy-3b-(4-trimethylstannylphenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose PET were enrolled. The 11C-CFT uptake was analyzed on both regional and voxel levels, whereas glucose metabolism was assessed in a voxel-wise fashion. Correlations between DAT and glucose metabolism imaging, DAT imaging and clinical severity, as well as glucose metabolism imaging and clinical severity were explored. Both clinical symptoms and DAT-binding patterns in the posterior putamen were highly symmetrical in patients with PRKN-EOPD, and dopaminergic dysfunction in the ipsilateral putamen was severer in patients with PRKN-EOPD than GU-EOPD. Meanwhile, the DAT binding was associated with the severity of motor dysfunction in patients with GU-EOPD only. Patients with PRKN-EOPD showed increased glucose metabolism in the contralateral medial frontal gyrus (supplementary motor area (SMA)), contralateral substantia nigra, contralateral thalamus, and contralateral cerebellum. Notably, glucose metabolic activity in the contralateral medial frontal gyrus was inversely associated with regional DAT binding in the bilateral putamen. Patients with PRKN-EOPD showed enhanced metabolic connectivity within the bilateral putamen, ipsilateral paracentral and precentral lobules, and the ipsilateral SMA. Collectively, compared to GU-EOPD, PRKN-EOPD is characterized by symmetrical, more severe dopaminergic dysfunction and relative increased glucose metabolism. Meanwhile, SMA with elevated glucose metabolism and enhanced connectivity may act as compensatory mechanisms in PRKN-EOPD.Supplementary informationThe online version contains supplementary material available at 10.1007/s43657-022-00077-8.

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Specific immune status in Parkinson's disease at different ages of onset.

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