Filamentous tau aggregates, the hallmark lesions of Alzheimer disease (AD), play key roles in neurodegeneration. Activation of protein degradation systems has been proposed to be a potential strategy for removing pathological tau, but it remains unclear how effectively tau aggregates can be degraded by these systems. By applying our previously established cellular model system of AD-like tau aggregate induction using preformed tau fibrils, we demonstrate that tau aggregates induced in cells with regulated expression of full-length mutant tau can be gradually cleared when soluble tau expression is suppressed. This clearance is at least partially mediated by the autophagy-lysosome pathway, although both the ubiquitin-proteasome system and the autophagy-lysosome pathway are deficient in handling large tau aggregates. Importantly, residual tau aggregates left after the clearance phase leads to a rapid reinstatement of robust tau pathology once soluble tau expression is turned on again. Moreover, we succeeded in generating monoclonal cells persistently carrying tau aggregates without obvious cytotoxicity. Live imaging of GFP-tagged tau aggregates showed that tau inclusions are dynamic structures constantly undergoing "fission" and "fusion," which facilitate stable propagation of tau pathology in dividing cells. These findings provide a greater understanding of cell-to-cell transmission of tau aggregates in dividing cells and possibly neurons.Filamentous aggregates made up of hyperphosphorylated tau protein are the defining pathological feature of numerous neurodegenerative diseases, such as Alzheimer disease, corticobasal degeneration, progressive supranuclear palsy, and Pick disease, which are collectively termed tauopathies (reviewed by Ref. 1). Physiologically, tau is a highly soluble microtubule-associated protein important for the assembly and stability of microtubules (2, 3). Insoluble, aggregated tau that is hyperphosphorylated and conformationally altered not only loses its physiological role of binding microtubules, but can also physically interfere with normal functioning of other cellular components (reviewed by Ref. 4). Strong correlations of the distribution and severity of tau pathology with clinical phenotypes of tauopathy patients (5-7) support the key contribution of aggregated tau to neuronal dysfunction and degeneration in these diseases, although some studies suggest pre-fibrillar tau species, such as oligomers, could be equally, if not more toxic than mature tau fibrils (8 -11).One obvious strategy to treat tauopathies is to remove intracellular tau aggregates either by promoting the disassembly of tau fibrils or by activating cellular degradation machineries to clear these toxic entities. A recent study demonstrated that it is possible to reverse mature tau inclusions together with associated neuronal deficits by suppressing soluble tau expression in a mouse model with inducible expression of tau, but the exact mechanism of tau pathology clearance was not explored (12). There are two primary pro...

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Background: Gastroparesis can be associated with severe symptoms. Health care utilization for gastroparesis has increased in part due to an increase in hospital admissions. Goals: To characterize patients admitted for gastroparesis-related symptoms and determine risk factors associated with 30-day readmissions. Study: The Nationwide Readmission Database (NRD) for the year 2014 was used to identify patients admitted to hospitals using the International Classification of Diseases (ICD)-9 code for gastroparesis as primary diagnosis or as the secondary diagnosis with first diagnosis code of a gastroparesisrelated symptom. Logistic regression was used to determine risk factors associated with 30-day readmission. Results: There were 5268 gastroparesis patients admitted with the average length of stay (LOS) of 5.4±6.6 days. Age averaged 48.9±18.1 years, 73.8% were female individuals, and 31% had diabetes. Inpatient mortality was 0.4%. The overall 30-day readmission rate was 6.2%. Longer LOS [odds ratio (OR)=1.4; 95% confidence interval (CI), 1.0-1.9], younger age, drug abuse (OR=1.6; 95% CI, 1.2-2.2), and marijuana use (OR=1.7; 95% CI, 1.0-2.7) were associated with increased risk of 30-day readmission. Female gender (P=0.083), opioid use (P=0.057), and admission to larger hospital (P=0.070) showed a trend toward higher readmission rates. Older patients, and patients with hypertension and diabetes showed lower rates of readmission. Conclusions: Use of the Nationwide Readmission Database (NRD) allows better understanding of gastroparesis admissions and readmissions. Average hospital stay was 5.4 days with 0.4% mortality rate. Overall 30-day readmission rate was 6.2%. Higher LOS, drug abuse, and marijuana use increased the 30-day readmission rate. Diabetes, hypertension, and older age were associated with lower readmissions.