Aberrant processing of the amyloid precursor protein (APP) and the subsequent accumulation of amyloid β (Aβ) peptide has been widely established as a central event in Alzheimer's disease (AD) pathogenesis. The sequential cleavage steps required for the generation of Aβ are well outlined; however, there is a relative dearth of knowledge pertaining to signaling pathways and molecular mechanisms that can modulate this process. Here, we demonstrate a novel role for p25/cyclin-dependent kinase 5 (Cdk5) in regulating APP processing, Aβ peptide generation, and intraneuronal Aβ accumulation in inducible p25 transgenic and compound PD–APP transgenic mouse models that demonstrate deregulated Cdk5 activity and a neurodegenerative phenotype. Induction of p25 resulted in enhanced forebrain Aβ levels before any evidence of neuropathology in these mice. Intracellular Aβ accumulated in perinuclear regions and distended axons within the forebrains of these mice. Evidence for modulations in axonal transport or β-site APP cleaving enzyme 1 protein levels and activity are presented as mechanisms that may account for the Aβ accumulation caused by p25/Cdk5 deregulation. Collectively, these findings delineate a novel pathological mechanism involving aberrant APP processing by p25/Cdk5 and have important implications in AD pathogenesis.

Depression, one of the most costly and common mental disorders, is reported to be associated with lower quality of life (QoL) in several studies. Improved understanding of the associated factors with QoL is necessary to optimize long-term outcomes and reduce disability in patients with depression. Therefore, the aim of this study was to identify factors that are associated with lower QoL among patients with depression. The study was based on the Korea National Health and Nutrition Examination Survey, a cross-sectional health examination, years 2008 to 2014. The final analyzed sample consisted of a total of 1,502 study subjects who had been diagnosed by clinicians as having depression. A multivariate logistic regression model was performed to exam the association between the clinical characteristics (age, sex, demographic and health-related characteristics) and QoL. Analysis of covariance was also used to analyze EQ-5D according to mental health. Older age, lower level of education, lower income, worse subjective perception of health, unemployment, obesity and mental health struggles were found to be significantly associated with low QoL in depressive individuals after adjustment for multiple covariates. This study has outlined grounding data in identifying patients who are at risk of QoL impairment. Policy makers should direct their interests to these individuals and provide appropriate management.

Background: The lack of adequate and detailed epidemiological data of Parkinson’s disease (PD), especially in Asia, is a barrier to future disease burdens and the prospect of effective public health plans. This study aimed to investigate temporal trends in the incidence and prevalence of PD in South Korea from 2010 to 2015, based on uniform diagnostic criteria. Methods: This study examined all PD patients registered in a South Korean national registry database of more than 50 million individuals. We analyzed the incidence and prevalence of PD according to age, gender, and region. Results: The annual incidence of PD was between 22.4–27.8 cases per 100,000 individuals. During the 6-year study period, there were 73,726 new PD patients, 42.3% of whom were men. The standardized incidence of PD increased over time in men but remained constant in women until 2013 but began to increase in 2014. The female-to-male ratio in the incidence of PD was 1.4:1 while the female-to-male ratio in the prevalence of PD was 1.6:1. The age- and gender-standardized prevalence of PD increased from 115.9 cases per 100,000 individuals in 2010 to 139.8 cases per 100,000 individuals in 2015. From 2014, the incidence and prevalence of PD peaked in individuals aged between 80 and 89 years in both men and women. Regional analysis also showed an increased prevalence of PD in all regions of Korea. Conclusions: The incidence and prevalence of PD in Korea were higher in women and increased gradually from 2010 to 2015. The findings may contribute to epidemiological studies of PD in Asia, and may provide clues on risk factors for PD.

Vitamin D deficiency and frailty are common with aging. Previous studies examining vitamin D status and frailty have produced mixed results, and in particular, the shape of the association has not been well established. We examined the association between 25-hydroxyvitamin D (25OHD) serum levels and frailty by performing a systematic review and dose-response meta-analysis. We searched the PubMed, EMBASE and Cochrane Library databases of Elsevier through February 2017. Cross-sectional and cohort studies that reported adjusted risk ratios with 95% confidence intervals (CI) for frailty with ≥3 categories of 25OHD serum levels were selected. Data extraction was performed independently by two authors. The reported risk estimates for 25OHD categories were recalculated, employing a comprehensive trend estimation from summarized dose-response data. The pooled risk estimate of frailty syndrome per 25 nmol/L increment in serum 25OHD concentration was 0.88 (95% CI = 0.82–0.95, I2 = 86.8%) in the 6 cross-sectional studies and 0.89 (95% CI = 0.85–0.94, I2 = 0.0%) in the 4 prospective cohort studies. Based on the Akaike information criteria (AIC), a linear model was selected (AIC for the nonlinear model: − 5.4, AIC for the linear model: − 6.8 in the prospective cohort studies; AIC for the linear model: − 13.6, AIC for the nonlinear model: − 1.77 in the cross-sectional studies). This dose-response meta-analysis indicates that serum 25OHD levels are significantly and directly associated with the risk of frailty. Further studies should address the underlying mechanisms to explain this relationship and to determine whether vitamin D supplementation is effective for preventing frailty syndrome.