Converging evidence suggests that the accumulation of cerebral amyloid beta-protein (Abeta) in Alzheimer's disease (AD) reflects an imbalance between the production and degradation of this self-aggregating peptide. Upregulation of proteases that degrade Abeta thus represents a novel therapeutic approach to lowering steady-state Abeta levels, but the consequences of sustained upregulation in vivo have not been studied. Here we show that transgenic overexpression of insulin-degrading enzyme (IDE) or neprilysin (NEP) in neurons significantly reduces brain Abeta levels, retards or completely prevents amyloid plaque formation and its associated cytopathology, and rescues the premature lethality present in amyloid precursor protein (APP) transgenic mice. Our findings demonstrate that chronic upregulation of Abeta-degrading proteases represents an efficacious therapeutic approach to combating Alzheimer-type pathology in vivo.

Currently, ≈1 in 13 people living in the United States has DM, and 90% to 95% of these individuals have type 2 DM (T2DM).2 Overall, the prevalence of T2DM is similar in women and men. In the United States, ≈12.6 million women (10.8%) and 13 million men (11.8%) ≥20 years of age are currently estimated to have T2DM. 2 Among individuals with T2DM, cardiovascular disease (CVD) is the leading cause of morbidity and mortality and accounts for >75% of hospitalizations and >50% of all deaths.3 Although nondiabetic women have fewer cardiovascular events than nondiabetic men of the same age, this advantage appears to be lost in the context of T2DM. 4,5 The reasons for this advantage are not entirely clear but are likely multifactorial with contributions from inherent physiological differences, including the impact of the sex hormones, differences in cardiovascular risk factors, and differences between the sexes in the diagnosis and treatment of DM and CVD. 6 In addition, there are racial and ethnic factors to consider because women of ethnic minority backgrounds have a higher prevalence of DM than non-Hispanic white (NHW) women.This scientific statement was designed to provide the current state of knowledge about sex differences in the cardiovascular consequences of DM, and it will identify areas that would benefit from further research because much is still unknown about sex differences in DM and CVD. Areas that are discussed include hormonal differences between the sexes and their possible effects on the interaction between DM and CVD, sex differences in epidemiology, ethnic and racial differences and risk factors for CVD in DM across the life span, sex differences in various types of CVD and heart failure, and sex differences in the effects of treatments for DM, including both medications and lifestyle. In addition, there is discussion about risk factors that are specific to women, including gestational diabetes mellitus (GDM) and polycystic ovarian syndrome (PCOS), which affect CVD risk. Table 1 focuses on sex differences in CVD risk factors and outcomes in DM, and Table 2 provides information about sex differences in CVD treatments and interventions in DM. Table 3 contains some of the important ideas for research in sex differences in the cardiovascular consequences of DM. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on July 31, 2015, and the American Heart Association Executive Committee on September 5, 2015. A copy of the document is available at http://my.americanheart.org/statements by selecting either the "By...

Among young women, measures of free testosterone were independently and inversely associated with BNP and NT-proBNP. These results suggest that circulating free testosterone, not estradiol, mediates gender differences in natriuretic peptides. In addition, the association between higher BMI and lean body mass with natriuretic peptides may be mediated by testosterone.

Following UUO, the co-localization of hypoxia with cellular proliferation, necrosis, and TBM thickening of the PT is consistent with ischemic injury resulting from vasoconstriction. In contrast, a selective dilation of the distal portion of the nephron (DT and CD), which results from the greater tubular compliance there, leads to stretch-induced epithelial cell apoptosis, along with a progressive peritubular fibrosis. Nephron loss in the obstructed developing kidney likely results from complex, segment-specific cellular responses.