α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson's disease.
- 作者列表："Lindestam Arlehamn CS","Dhanwani R","Pham J","Kuan R","Frazier A","Rezende Dutra J","Phillips E","Mallal S","Roederer M","Marder KS","Amara AW","Standaert DG","Goldman JG","Litvan I","Peters B","Sulzer D","Sette A
:A diagnosis of motor Parkinson's disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis.
: 运动性帕金森病 (PD) 的诊断之前是延长的前运动相，伴随着累积的神经元损伤。在这里，我们检查了 α-突触核蛋白 (α-syn) T细胞反应性和PD之间的时间关系。纵向病例研究显示，在诊断运动PD之前检测到升高的 α-syn特异性T细胞应答，之后下降。两个独立队列中T细胞反应性和早期PD之间的关系显示，α-syn特异性T细胞反应在诊断运动PD后不久最高，然后下降。另外的分析显示 α-syn特异性T细胞应答与age和较低的左旋多巴等效剂量显著相关。这些结果证实了 α-syn反应性T细胞在PD中的存在，并显示它们在诊断运动PD后立即最丰富。这些细胞可能在诊断运动PD之前存在数年，这表明研究PD发病机制和潜在早期诊断的途径。
METHODS:BACKGROUND:Whether vitamin D receptor (VDR) genetic variants influence individual susceptibility to neurodegenerative disorders remains controversial. AIMS:This meta-analysis was conducted to analyze correlations of VDR genetic variants with two types of most common neurodegenerative disorders, Parkinson's disease (PD) and Alzheimer's disease (AD). METHODS:Systematic literature research of PubMed and Embase was performed to identify eligible articles. Q test and I2 statistic were employed to decide whether pooled analyses would be performed with random-effect models (REMs) or fixed-effect models (FEMs). All statistical analyses were conducted with Review Manager. RESULTS:Totally sixteen studies were enrolled for analyses. Among these eligible studies, ten studies were about PD (2356 cases and 2815 controls) and six studies were about AD (1256 cases and 1205 controls). Pooled overall analyses suggested that VDR rs7975232 (additive model: p = 0.03, OR = 1.19, 95% CI 1.01-1.39) and rs2228570 (recessive model: p < 0.008, OR = 1.26, 95% CI 1.06-1.50; allele model: p < 0.001, OR = 0.80, 95% CI 0.71-0.91) variants were significantly correlated with PD, and VDR rs731236 (dominant model: p = 0.003, OR = 0.70, 95% CI 0.56-0.89; additive model: p = 0.02, OR = 1.32, 95% CI 1.06-1.66; allele model: p = 0.02, OR = 0.82, 95% CI 0.69-0.96) variant was significantly correlated with AD. Further subgroup analyses by ethnicity revealed that the positive results were mainly driven by the Asians, whereas no significant associations were observed in Caucasians. CONCLUSION:Our meta-analysis suggested that VDR rs7975232 and rs2228570 variants might serve as genetic biomarkers of PD, whereas VDR rs731236 variant might serve as a genetic biomarker of AD.
METHODS::Elderly people can be provided with safer and more independent living by the early detection of abnormalities in their performing actions and the frequent assessment of the quality of their motion. Low-cost depth sensing is one of the emerging technologies that can be used for unobtrusive and inexpensive motion abnormality detection and quality assessment. In this study, we develop and evaluate vision-based methods to detect and assess neuromusculoskeletal disorders manifested in common daily activities using three-dimensional skeletal data provided by the SDK of a depth camera (e.g., MS Kinect and Asus Xtion PRO). The proposed methods are based on extracting medically -justified features to compose a simple descriptor. Thereafter, a probabilistic normalcy model is trained on normal motion patterns. For abnormality detection, a test sequence is classified as either normal or abnormal based on its likelihood, which is calculated from the trained normalcy model. For motion quality assessment, a linear regression model is built using the proposed descriptor in order to quantitatively assess the motion quality. The proposed methods were evaluated on four common daily actions-sit to stand, stand to sit, flat walk, and gait on stairs-from two datasets, a publicly released dataset and our dataset that was collected in a clinic from 32 patients suffering from different neuromusculoskeletal disorders and 11 healthy individuals. Experimental results demonstrate promising results, which is a step toward having convenient in-home automatic health care services.
METHODS:BACKGROUND:Parkinson's disease (PD) is responsible for significant changes in body composition. AIMS:We aimed to test the association between PD severity and fat distribution patterns, and to investigate the potential modifier effect of nutritional status in this association. METHODS:We enrolled 195 PD subjects consecutively admitted to a university geriatric day hospital. All participants underwent comprehensive clinical evaluation, including assessment of total and regional body composition (dual-energy X-ray absorptiometry, DXA), body mass index, nutritional status (Mini-Nutritional Assessment, MNA), motor disease severity (UPDRS III), comorbidities, and pharmacotherapy. RESULTS:The fully adjusted linear regression model showed a negative association between UPDRS III and total body fat in kg and percentage (respectively, B - 0.79; 95% CI - 1.54 to - 0.05 and B - 0.55; 95% CI - 1.04 to - 0.05), percentage android fat (B - 1.07; 95% CI - 1.75 to - 0.39), trunk-leg fat ratio (B - 0.02; 95% CI - 0.04 to - 0.01), trunk-limb fat ratio (B - 0.01; 95% CI - 0.06 to - 0.01) and android-gynoid fat ratio (B - 0.01; 95% CI - 0.03 to - 0.01). After stratification by MNA score, all the parameters of android-like fat distribution resulted negatively associated (p < 0.001 for all) with UPDRS III, but only among subjects with a MNA < 23.5 (risk of malnutrition or malnutrition). CONCLUSION:We found a negative association between severity of motor impairment and total fat mass in PD, more specific with respect to an android pattern of fat distribution. This association seems to be driven by nutritional status, and is significant only among patients at risk of malnutrition or with overt malnutrition.