Genetic susceptibility modifies the association of long-term air pollution exposure on Parkinson's disease.

Inconsistent findings exist regarding the potential association between polluted air and Parkinson's disease (PD), with unclear insights into the role of inherited sensitivity. This study sought to explore the potential link between various air pollutants and PD risk, investigating whether genetic susceptibility modulates these associations. The population-based study involved 312,009 initially PD-free participants with complete genotyping data. Annual mean concentrations of PM2.5, PM10, NO2, and NOx were estimated, and a polygenic risk score (PRS) was computed to assess individual genetic risks for PD. Cox proportional risk models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between ambient air pollutants, genetic risk, and incident PD. Over a median 12.07-year follow-up, 2356 PD cases (0.76%) were observed. Compared to the lowest quartile of air pollution, the highest quartiles of NO2 and PM10 pollution showed HRs and 95% CIs of 1.247 (1.089-1.427) and 1.201 (1.052-1.373) for PD incidence, respectively. Each 10 µg/m3 increase in NO2 and PM10 yielded elevated HRs and 95% CIs for PD of 1.089 (1.026-1.155) and 1.363 (1.043-1.782), respectively. Individuals with significant genetic and PM10 exposure risks had the highest PD development risk (HR: 2.748, 95% CI: 2.145-3.520). Similarly, those with substantial genetic and NO2 exposure risks were over twice as likely to develop PD compared to minimal-risk counterparts (HR: 2.414, 95% CI: 1.912-3.048). Findings suggest that exposure to air contaminants heightens PD risk, particularly in individuals genetically predisposed to high susceptibility.

Plasma ß2-microglobulin and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact older adults: the CABLE study.

BACKGROUND: Previous studies have suggested a correlation between elevated levels of ß2-microglobulin (B2M) and cognitive impairment. However, the existing evidence is insufficient to establish a conclusive relationship. This study aims to analyze the link of plasma B2M to cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers and cognition. METHODS: To track the dynamics of plasma B2M in preclinical AD, 846 cognitively healthy individuals in the Chinese Alzheimer's Biomarker and LifestylE (CABLE) cohort were divided into four groups (suspected non-AD pathology [SNAP], 2, 1, 0) according to the NIA-AA criteria. Multiple linear regression models were employed to examine the plasma B2M's relationship with cognitive and CSF AD biomarkers. Causal mediation analysis was conducted through 10,000 bootstrapped iterations to explore the mediating effect of AD pathology on cognition. RESULTS: We found that the levels of plasma B2M were increased in stages 1 (P = 0.0007) and 2 (P < 0.0001), in contrast to stage 0. In total participants, higher levels of B2M were associated with worse cognitive performance (P = 0.006 for MMSE; P = 0.012 for MoCA). Moreover, a higher level of B2M was associated with decreases in Aß1-42 (P < 0.001) and Aß1-42/Aß1-40 (P = 0.015) as well as increases in T-tau/Aß1-42 (P < 0.001) and P-tau/Aß1-42 (P < 0.001). The subgroup analysis found B2M correlated with Aß1-42 in non-APOE ε4 individuals (P < 0.001) but not in APOE ε4 carriers. Additionally, the link between B2M and cognition was partially mediated by Aß pathology (percentage: 8.6 to 19.3%), whereas tau pathology did not mediate this effect. CONCLUSIONS: This study demonstrated the association of plasma B2M with CSF AD biomarkers as well as a possible important role of Aß pathology in the association between B2M and cognitive impairment, particularly in cognitively normal individuals. The results indicated that B2M could be a potential biomarker for preclinical AD and might have varied functions throughout various stages of preclinical AD progression.

Differences between ante mortem Alzheimer's disease biomarkers in predicting neuropathology at autopsy.

INTRODUCTION: This study aimed to assess whether biomarkers related to amyloid, tau, and neurodegeneration can accurately predict Alzheimer's disease (AD) neuropathology at autopsy in early and late clinical stages. METHODS: We included 100 participants who had ante mortem biomarker measurements and underwent post mortem neuropathological examination. Based on ante mortem clinical diagnosis, participants were divided into non-dementia and dementia, as early or late clinical stages. RESULTS: Amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) amyloid beta (Aß)42/phosphorylated tau (p-tau)181 showed excellent performance in differentiating autopsy-confirmed AD and predicting the risk of neuropathological changes in early and late clinical stages. However, CSF Aß42 performed better in the early clinical stage, while CSF p-tau181, CSF t-tau, and plasma p-tau181 performed better in the late clinical stage. DISCUSSION: Our findings provide important clinical information that, if using PET, CSF, and plasma biomarkers to detect AD pathology, researchers must consider their differential performances at different clinical stages of AD. HIGHLIGHTS: Amyloid PET and CSF Aß42/p-tau181 were the most promising candidate biomarkers for predicting AD pathology. CSF Aß42 can serve as a candidate predictive biomarker in the early clinical stage of AD. CSF p-tau181, CSF t-tau, and plasma p-tau181 can serve as candidate predictive biomarkers in the late clinical stage of AD. Combining APOE ε4 genotypes can significantly improve the predictive accuracy of AD-related biomarkers for AD pathology.

Sleep duration and risk of cardio-cerebrovascular disease: A dose-response meta-analysis of cohort studies comprising 3.8 million participants.

Background: The effect of extreme sleep duration on the risk of cardiovascular and cerebrovascular diseases (CCDs) remains debatable. The pathology of CCDs is consistent in some respects (e.g., vascular factors), suggesting that there may be an overlapping range of sleep duration associated with a low risk of both diseases We aimed to quantify the dose-response relationship between sleep duration and CCDs. Study objective: To explore whether there is an optimal sleep duration (SD) in reducing the risk of CCDs. Methods: PubMed and EMBASE were searched until June 24, 2022 to include cohort studies that investigated the longitudinal relationships of SD with incident CCDs, including stroke and coronary heart disease (CHD). The robusterror meta-regression model (REMR model) was conducted to depict the dose-response relationships based on multivariate-adjusted risk estimates. Results: A total of 71 cohorts with 3.8 million participants were included for meta-analysis, including 57 for cardiovascular diseases (CVD) and 29 for cerebrovascular disease. A significant U-shaped relationship was revealed of nighttime sleep duration with either cardiovascular or cerebrovascular disease. The nighttime sleep duration associated with a lower risk of CVD was situated within 4.3-10.3 h, with the risk hitting bottom at roughly 7.5 h per night (p non-linearity < 0.0001). Sleep duration associated with a lower risk of cerebrovascular diseases ranges from 5 to 9.7 h per night, with the inflection at 7.5 h per night (p non-linearity = 0.05). Similar non-linear relationship exited in daily sleep duration and CCDs. Other subgroup analyses showed non-linear relationships close to the above results. Conclusion: Rational sleep duration (7.5 h/night) is associated with a reduced risk of cardio-cerebrovascular disease for adults.

Association of peripheral immunity with cognition, neuroimaging, and Alzheimer's pathology.

BACKGROUND: Neuroinflammation has been considered to be a driving force of Alzheimer's disease. However, the association between peripheral immunity and AD has been rarely investigated. METHODS: Separate regression analyses were conducted to explore the associations among peripheral immune markers and cognition, neuroimaging, and AD pathology. Causal mediation analyses were used to investigate whether the associations with cognition were mediated by AD pathology. RESULTS: A total of 1107 participants (43.9% female, mean age of 73.2 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were included. Regression analyses indicated that elevated neutrophils (NEU) count and neutrophil-lymphocyte ratio (NLR) were associated with lower levels of global cognition, memory function (MEM), and executive function (EF), and reduced brain metabolism by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) as well as greater ventricular volume. An elevated NLR was associated with a lower level of ß-amyloid (Aß) and a higher level of total tau (T-tau) in cerebrospinal fluid (CSF), smaller hippocampal volume (HV), and lesser entorhinal cortex (EC) thickness. On the contrary, an elevated level of lymphocytes (LYM) was associated with a higher level of Aß and a lower level of T-tau in CSF, better cognition, and less atrophy of brain regions (ventricular volume, HV, and EC thickness). The associations of LYM and NLR with cognition were mediated by Aß and T-tau pathology (proportion: 18%~64%; p < 0.05). CONCLUSIONS: We revealed that two types of peripheral immune cells (NEU and LYM) and the ratio of these two cell types (NLR) had associations with cognition, neuroimaging, and AD pathology. The associations might be mediated by Aß and tau pathology.

Complete genome sequence of human pathogen Kosakonia cowanii type strain 888-76T

ABSTRACT Kosakonia cowanii type strain 888-76T is a human pathogen which was originally isolated from blood as NIH group 42. In this study, we report the complete genome sequence of K. cowanii 888-76T. 888-76T has 1 chromosome and 2 plasmids with a total genome size of 4,857,567 bp and C+G 56.15%. This genome sequence will not only help us to understand the virulence features of K. cowanii 888-76T but also provide us the useful information for the study of evolution of Kosakonia genus.

Complete genome sequence of human pathogen Kosakonia cowanii type strain 888-76T.

Kosakonia cowanii type strain 888-76T is a human pathogen which was originally isolated from blood as NIH group 42. In this study, we report the complete genome sequence of K. cowanii 888-76T. 888-76T has 1 chromosome and 2 plasmids with a total genome size of 4,857,567bp and C+G 56.15%. This genome sequence will not only help us to understand the virulence features of K. cowanii 888-76T but also provide us the useful information for the study of evolution of Kosakonia genus.

Draft Genome Sequence of Klebsiella pneumoniae Strain AS Isolated from Zhejiang Provincial Hospital of TCM, China.

Klebsiella pneumoniae is a Gram-negative, nonmotile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. Here we present draft genome assemblies of Klebsiella pneumoniae AS, which was isolated in China. The genomic information will provide a better understanding of the physiology, adaptation, and evolution of K. pneumoniae.