Molecular cross talk between misfolded proteins in animal models of Alzheimer's and prion diseases.

The central event in protein misfolding disorders (PMDs) is the accumulation of a misfolded form of a naturally expressed protein. Despite the diversity of clinical symptoms associated with different PMDs, many similarities in their mechanism suggest that distinct pathologies may cross talk at the molecular level. The main goal of this study was to analyze the interaction of the protein misfolding processes implicated in Alzheimer's and prion diseases. For this purpose, we inoculated prions in an Alzheimer's transgenic mouse model that develop typical amyloid plaques and followed the progression of pathological changes over time. Our findings show a dramatic acceleration and exacerbation of both pathologies. The onset of prion disease symptoms in transgenic mice appeared significantly faster with a concomitant increase on the level of misfolded prion protein in the brain. A striking increase in amyloid plaque deposition was observed in prion-infected mice compared with their noninoculated counterparts. Histological and biochemical studies showed the association of the two misfolded proteins in the brain and in vitro experiments showed that protein misfolding can be enhanced by a cross-seeding mechanism. These results suggest a profound interaction between Alzheimer's and prion pathologies, indicating that one protein misfolding process may be an important risk factor for the development of a second one. Our findings may have important implications to understand the origin and progression of PMDs.

Concomitant Mycobacterium tuberculosis infection and type 2 diabetes: A descriptive model with global health implications

The type 2 diabetes (diabetes) pandemic is recognized as a threat to tuberculosis (TB) control worldwide. This secondary data analysis project estimated the contribution of diabetes to TB in a binational community on the Texas-Mexico border where both diseases occur. Newly-diagnosed TB patients > 20 years of age were prospectively enrolled at Texas-Mexico border clinics between January 2006 and November 2008. Upon enrollment, information regarding social, demographic, and medical risks for TB was collected at interview, including self-reported diabetes. In addition, self-reported diabetes was supported by blood-confirmation according to guidelines published by the American Diabetes Association (ADA). For this project, data was compared to existing statistics for TB incidence and diabetes prevalence from the corresponding general populations of each study site to estimate the relative and attributable risks of diabetes to TB. In concordance with historical sociodemographic data provided for TB patients with self-reported diabetes, our TB patients with diabetes also lacked the risk factors traditionally associated with TB (alcohol abuse, drug abuse, history of incarceration, and HIV infection); instead, the majority of our TB patients with diabetes were characterized by overweight/obesity, chronic hyperglycemia, and older median age. In addition, diabetes prevalence among our TB patients was significantly higher than in the corresponding general populations. Findings of this study will help accurately characterize TB patients with diabetes, thus aiding in the timely recognition and diagnosis of TB in a population not traditionally viewed as at-risk. We provide epidemiological and biological evidence that diabetes continues to be an increasingly important risk factor for TB.^