BIN1 is the most significant late-onset Alzheimer’s Disease (AD) susceptibility locus identified via genome-wide association studies. BIN1 is an adaptor protein that regulates membrane dynamics in the context of endocytosis and membrane remodeling. An increase in BIN1 expression and changes in the relative levels of alternatively-spliced BIN1 isoforms have been reported in the brains of patients with AD. BIN1 can bind to Tau, and an increase of BIN1 expression correlates with Tau pathology. In contrast, the loss of BIN1 expression in cultured cells elevates Aβ production and Tau propagation by influencing endocytosis and recycling. Here we show that BIN1 accumulates adjacent to amyloid deposits in vivo. We found an increase in insoluble BIN1 and a striking accrual of BIN1 within and near amyloid deposits in the brains of multiple transgenic models of AD. The peri-deposit aberrant BIN1 localization was conspicuously different from the accumulation of APP and BACE1 within dystrophic neurites. Although BIN1 is highly expressed in mature oligodendrocytes, BIN1 association with amyloid deposits occurred in the absence of the accretion of other oligodendrocyte or myelin proteins. Finally, super-resolution microscopy and immunogold electron microscopy analyses highlight the presence of BIN1 in proximity to amyloid fibrils at the edges of amyloid deposits. These results reveal the aberrant accumulation of BIN1 is a feature associated with AD amyloid pathology. Our findings suggest a potential role for BIN1 in extracellular Aβ deposition in vivo that is distinct from its well-characterized function as an adaptor protein in endocytosis and membrane remodeling.
Pandemics are difficult times for the mental health of healthcare professionals, who are more likely to present with PTSD-like symptoms. In the context of a highly contagious communicable disease, telemedicine is a useful alternative to usual care, and should be considered as a means to support healthcare professionals’ mental health. This is a multicenter (n = 19), cross-sectional study, based on a 27-item questionnaire, aiming to investigate the acceptability to healthcare workers of a telepsychiatry service as a means of providing mental health support during the COVID-19 pandemic. Between October and December 2020, 321 responses were received, showing that women, caregiving staff, and those directly involved in the care of COVID-19 patients are less favorable to the idea of receiving remote support. In our population, barriers were related to the clinical setting or ethics, and most of the respondents would not accept a drug prescription by telepsychiatry. Although telepsychiatry should be a part of the armamentarium of mental health management, it is not suitable as a stand-alone approach, and should be combined with conventional face-to-face consultations.
Background Nursing homes (NHs) have been particularly affected by COVID-19. The aim of this study is to estimate the burden of COVID-19 and to investigate factors associated with mortality during the first epidemic wave in a large French NHs network. Methods An observational cross-sectional study was conducted in September-October 2020. 290 NHs were asked to complete an online questionnaire covering the first epidemic wave on facilities and resident characteristics, number of suspected/confirmed COVID-19 deaths, and preventive/control measures taken at the facility level. Data were crosschecked using routinely collected administrative data on the facilities. The statistical unit of the study was the NH. Overall COVID-19 mortality rate was estimated. Factors associated with COVID-19 mortality were investigated using a multivariable multinomial logistic regression. The outcome was classified in 3 categories: “no COVID-19 death in a given NH”, occurrence of an “episode of concern” (at least 10% of the residents died from COVID-19), occurrence of a “moderate episode” (deaths of COVID-19, less than 10% of the residents). Results Of the 192 (66%) participating NHs, 28 (15%) were classified as having an “episode of concern”. In the multinomial logistic regression, moderate epidemic magnitude in the NHs county (adjusted OR = 9.3; 95%CI=[2.6–33.3]), high number of healthcare and housekeeping staff (aOR = 3.7 [1.2–11.4]) and presence of an Alzheimer’s unit (aOR = 0.2 [0.07–0.7]) were significantly associated with an “episode of concern”. Conclusions We found a significant association between the occurrence of an “episode of concern” in a NH and some of its organizational characteristics and the epidemic magnitude in the area. These results can be used to improve the epidemic preparedness of NHs, particularly regarding the organization of NHs in small units with dedicated staff. Brief summary Factors associated with COVID-19 mortality and preventive measures taken in nursing homes in France during the first epidemic wave.
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