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INTRODUCTION: A wide array of post‐translational modifications of the tau protein occurs in Alzheimer's disease (AD) and they are critical to pathogenesis and biomarker development. Several promising tau markers, pT181, pT217, and pT231, rely on increased phosphorylation within a common molecular motif threonine‐proline‐proline (TPP). METHODS: We validated new and existing antibodies against pT217, pT231, pT175, and pT181, then combined immunohistochemistry (IHC) and immunoassays (ELISA) to broadly examine the phosphorylation of the tau TPP motif in AD brains. RESULTS: The tau burden, as examined by IHC and ELISA, correlates to Braak stages across all TPP sites. Moreover, we observed regional variability across four TPP motif phosphorylation sites in multiple brains of sporadic AD patients. DISCUSSION: We conclude that there is an elevation of TPP tau phosphorylation in AD brains as disease advances. The regional variability of pTPP tau suggests that examining different phosphorylation sites is essential for a comprehensive assessment of tau pathology. [ABSTRACT FROM AUTHOR]

Objective: Endogenous Cushing's syndrome (CS) is a known cause of secondary osteoporosis. Vertebral fractures (VFs) in endogenous CS may occur despite normal bone mineral density (BMD). Trabecular bone score (TBS) is a relatively new, non‐invasive technique to assess bone microarchitecture. The objective of our study was to analyse the BMD and bone microarchitecture using TBS in endogenous CS and compare it with a group of age and sex‐matched healthy controls, and also analyse the factors predicting BMD and TBS. Design: Cross‐sectional study of cases and controls. Patients and measurements: We included 40 female patients with overt endogenous CS, out of which 32 were adrenocorticotropic hormone (ACTH)‐dependent CS and 8 were ACTH‐independent. We also included 40 healthy, female controls. Both patients and controls were subjected to an assessment of biochemical parameters and BMD and TBS. Results: Patients with endogenous CS had significantly lower BMD at the lumbar spine, femoral neck, and total hip and significantly lower TBS than healthy controls (all p <.001), while no significant difference was noted in the distal radius BMD (p =.055). In endogenous CS, a large proportion of patients, n = 13 (32.5%) had normal BMD for age (BMD Z‐score ≥ −2.0) with low TBS (L1‐L4 TBS ≤ 1.34). TBS correlated negatively with HbA1c (p =.006), and positively with serum T4 (p =.027). Conclusion: TBS should be considered an important complementary tool in addition to BMD for the routine assessment of skeletal health in CS. [ABSTRACT FROM AUTHOR]

Background: Despite being the most common cause of secondary hypertension, prevalence of primary aldosteronism (PA) among patients with young‐onset hypertension (YH ‐ age of hypertension onset <40 years) remains poorly studied. Objective: We assessed the prevalence of PA in patients with YH referred for evaluation of secondary hypertension. Design and Patients: In this prospective, cross‐sectional study, 202 patients with YH, visiting endocrine and cardiology clinics of All India Institute of Medical Sciences, India, were evaluated. Measurements: Primary aldosteronism was screened by measuring plasma aldosterone concentration (PAC) and direct renin concentration (DRC) and calculating aldosterone‐to‐renin ratio (ARR), followed by confirmatory saline infusion test (SIT) according to Endocrine Society Guideline. Those confirmed with post‐SIT PAC >5 ng/dl underwent adrenal computed tomography (CT), followed by adrenal venous sampling (AVS). Results: Of 202 YH patients, 38 (18.8%) screened positive, and PA was confirmed in 36 (17.8%). The mean age was 43.9 ± 10.9 years, and median duration of hypertension was 10.5 (3.5–18) years. The prevalence of PA increased with grade of hypertension (8.1% in grade 1 to 37.1% in grade 3), number of antihypertensive medications (2.5% in those taking ≤1 to 50% in those taking ≥4 medications) and severity of hypokalaemia (0% in potassium >5 to 85.7% in potassium <3.5 mmol/L). The prevalence of PA by age of hypertension onset was highest in age group 30–39 years (31.3%). Conclusions: There is a high prevalence and a long delay in diagnosis of PA among patients with YH, and YH should be considered as a separate high‐risk category in PA screening algorithm. [ABSTRACT FROM AUTHOR]