Objective Gut microbiota changes before the onset of Alzheimer's disease (AD) and the alterations could be detected in the stage of mild cognitive impairment (MCI). The findings might offer diagnostic biomarkers before the onset of dementia. Background AD is the most common cause of dementia, and MCI is the predementia state. Recent studies suggest the alterations in the gut microbial communities associated with AD, whereas the microbiota in MCI before the onset of dementia has not been discovered and characterized in humans. New/Updated Hypothesis We hypothesize that the dysbiosis happens in the MCI stage. Patients with AD and MCI have decreased microbial diversity, and changes in gut microbiota could be detected for early detection of AD. In our preliminary study, we identified differences between AD and normal controls in 11 genera from the feces and 11 genera from the blood. No difference in genera between AD and MCI was detected. Using the diagnostic model from fecal samples with all different genera input, 93% (28 in 30) of patients with MCI could be identified correctly. Major Challenges for the Hypothesis The diagnosis of MCI and AD in the study was based on symptoms and neuroimaging, and AD biomarkers should be included for precise diagnosis in further validating studies. Besides, as the microbiota changes longitudinally, their relationship with the progress of dementia needs to be studied in the prospective studies. Linkage to Other Major Theories Escherichia was observed increased at genus level in both fecal and blood samples from AD and MCI. For AD biomarker, postmortem brain tissue from patients with AD showed lipopolysaccharides and gram‐negative Escherichia coli fragments colocalize with amyloid plaque. In this way, the amyloid pathogenesis for AD would be triggered during MCI by gut microbiota shifting. Besides, systemic inflammatory reactions caused by compounds secreted by bacteria may impair the blood‐brain barrier and promote neuroinflammation and/or neurodegeneration. Furthermore, abnormal metabolites caused by microbial gene functions have an impact on neurodegeneration.

Our findings demonstrated the neuroprotective effect of Cb in TBI mice and the involved mechanisms were partially attributed to the elevating GLP-1 secretion through the gut-brain axis.

Background: Anxiety and depression are common in Parkinson disease and both are important determinants of quality of life in patients. Several risk factors are identified but few research have investigated general and Parkinson's disease (PD)-specific factors comprehensively. The aim of this work was to explore PD-specific and -non-specific risk factors for PD with depression or anxiety. Methods: A cross-sectional survey was performed in 403 patients with PD. Multivariate logistic analysis was used to investigate the prevalence and risk factors for the depression and anxiety in PD. The data of patients included demographic information, medicine history, disease duration, age at onset (AAO), family history, anti-parkinsonism drug, modified Hoehn and Yahr staging (H-Y) stage, scales of motor and non-motor symptoms and substantia nigra (SN) echogenic areas. Results: 403 PD patients were recruited in the study. Depression and anxiety were present in 11.17% and 25.81% respectively. Marital status, tumor, higher Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) II score, dyskinesia, higher Hamilton Anxiety Rating Scale (HARS) score and lower the Parkinson's disease sleep scale (PDSS) score were associated with depression in PD. female gender, higher rapid eye movement behavior disorder Questionnaire-Hong Kong (RBD-HK) score, higher Hamilton Deprssion Rating Scale (HAMD) score, higher the scale for outcomes in PD for autonomic symptoms (SCOPA-AUT)score and larger SN echogenic areas were associated with anxiety. Neither depression nor anxiety was related to any anti-parkinsonism drugs. Conclusions: The prevalence of depression and anxiety in the current PD patients was 11.17% and 25.81% respectively. Disease of tumor, currently having no partner, severer motor function, dyskinesia, poorer sleep quality and anxiety were risk factors for PD with depression. Female, depression, rapid eye movement behavior disorder (RBD), autonomic dysfunction and larger SN area were risk factors for PD with anxiety.

Identification of the gut microbiome compositions associated with disease has become a research focus worldwide. Emerging evidence has revealed the presence of gut microbiota dysbiosis in Parkinson’s disease. In this study, we aimed to identify the gut microbiome associated with Parkinson’s disease and subsequently to screen and to validate potential diagnostic biomarkers of Parkinson’s disease. This case-control study investigated gut microbial genes in faeces from 40 volunteer Chinese patients with Parkinson’s disease and their healthy spouses using shotgun metagenomic sequencing. Furthermore, the identified specific gut microbial gene markers were validated with real-time PCR in an independent Chinese cohort of 78 Parkinson’s disease patients, 75 control subjects, 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease. We developed the first gut microbial gene catalogue associated with Parkinson’s disease. Twenty-five gene markers were identified that distinguished Parkinson’s disease patients from healthy control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.896 (95% confidence interval: 83.1–96.1%). A highly accurate Parkinson’s disease index, which was not influenced by disease severity or Parkinson’s disease medications, was created. Testing these gene markers using quantitative PCR distinguished Parkinson’s disease patients from healthy controls not only in the 40 couples (AUC = 0.922, 95% confidence interval: 86.4–98.0%), but also in an independent group of 78 patients with Parkinson’s disease and 75 healthy control subjects (AUC = 0.905, 95% confidence interval: 86.0–95.1%). This classifier also performed a differential diagnosis power in discriminating these 78 patients with Parkinson’s disease from a cohort of 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease based on the panel of 25 biomarkers. Based on our results, the identified Parkinson’s disease index based on the gene set from the gut microbiome may be a potential diagnostic biomarker of Parkinson’s disease.

The rhodium-catalyzed intermolecular direct C-H thiolation of arenes with aryl and alkyl disulfides was developed for the first time to provide a convenient route to aryl thioethers. This strategy is compatible with many different directing groups and exhibits excellent functional group tolerance. More significantly, mono- or dithiolation can be selectively achieved, thus providing a straightforward way for selective preparation of aryl thioethers and dithioethers.

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Study Objectives: The aim of the study was to investigate the relationship between 22 single nucleotide polymorphisms (SNPs) and Parkinson’s disease (PD) in the Chinese population.Methods: A total of 250 PD patients and 240 healthy controls were recruited. The SNaPshot technique and the polymer chain reaction were used to detect 22 SNPs.Results: rs8005172 of GALC, rs9468199 of ZNF184 and rs34043159 of IL1R2, were associated with PD (rs8005172: p = 0.009, OR = 0.69, allele model, p = 0.010, additive model, p = 0.015, OR = 2.17, dominant model; p = 0.020, OR = 2.11, dominant model after adjustment; p = 0.036, OR = 1.47, recessive model after adjustment; rs9468199: p = 0.008, OR = 1.52, allele model, p = 0.008, additive model, p = 0.007, OR = 0.22, recessive model, p = 0.005, OR = 0.20, recessive model after adjustment; rs34043159: p = 0.034, OR = 1.31, allele model, p = 0.036, additive model).Conclusion: Our study revealed that GALC, ZNF184, and IL1R2 were associated with PD in the southern Chinese population. GALC was also associated with LOPD. ELOVL7 and ZNF184 were associated with EOPD. In addition, trends of association to PD, between SATB1, NMD3, and FGF20, were also found.Statement of Significance: Genetic play an important role in the pathogenesis factors of Parkinson’s disease (PD). We found that GALC, ZNF184, and IL1R2 were associated with PD. GALC was also associated with late onset of PD, while ELOVL7 and ZNF184 were associated with early onset PD. This study is the first to find an association between GALC, ZNF184, and rs2280104 with PD.

There is a high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson’s disease (PD) patients, but a Chinese version of cognitive rating scale that is specific and sensitive to PD patients is still lacking. The aims of this study are to test the reliability and validity of a Chinese version of Parkinson’s disease-cognitive rating scale (PD-CRS), establish cutoff scores for diagnosis of Parkinson’s disease dementia (PDD) and PD with mild cognitive impairment (PD-MCI), explore cognitive profiles of PD-MCI and PDD, and find cognitive deficits suggesting a transition from PD-MCI to PDD. PD-CRS was revised based on the culture background of Chinese people. Ninety-two PD patients were recruited in three PD centers and were classified into PD with normal cognitive function (PD-NC), PD-MCI, and PDD subgroups according to the cognitive rating scale (CDR). Those PD patients underwent PD-CRS blind assessment by a separate neurologist. The PD-CRS showed a high internal consistency (Cronbach’s Alpha = 0.840). Intraclass Correlation coefficient (ICC) of test-retest reliability reached 0.906 (95% CI 0.860–0.935, p<0.001). ICC of inter-rater reliability was 0.899 (95% CI 0.848–0.933, p<0.001). PD-CRS had fair concurrent validity with MDRS (ICC = 0.731, 95% CI 0.602–0.816). All the frontal-subcortical items showed significant decrease in PD-MCI compared with the PD-NC group (p≤0.001), but the instrument cortical items did not (confrontation naming p=0.717, copying a clock p=0.620). All the frontal-subcortical and instrumental-cortical functions showed significant decline in PDD compared with the PD-NC group (p≤0.001). The cutoff value for diagnosis of PD-MCI is 80.5 with the sensitivity of 75.7% and the specificity of 75.0%, and for diagnosis of PDD is 73.5 with the sensitivity of 89.2% and the specificity of 98.9%. Revised Chinese version of PD-CRS is a reliable, acceptable, valid, and useful neuropsychological battery for assessing cognition in PD patients.