Tau protein abnormally aggregates in tauopathies, a diverse group of neurologic diseases that includes Alzheimer's disease (AD). In early stages of disease, tau becomes hyperphosphorylated and mislocalized, which can contribute to its aggregation and toxicity. We demonstrate that tau phosphorylation at Ser208 (pSer208) promotes microtubule dysfunction and tau aggregation in cultured cells. Comparative assessment of the epitopes recognized by antibodies AT8, CP13, and 7F2 demonstrates that CP13 and 7F2 are specific for tau phosphorylation at Ser202 and Thr205, respectively, independently of the phosphorylation state of adjacent phosphorylation sites. Supporting the involvement of pSer208 in tau pathology, a novel monoclonal antibody 3G12 specific for tau phosphorylation at Ser208 revealed strong reactivity of tau inclusions in the brains of PS19 and rTg4510 transgenic mouse models of tauopathy. 3G12 also labelled neurofibrillary tangles in brains of patients with AD but revealed differential staining compared to CP13 and 7F2 for other types of tau pathologies such as in neuropil threads and neuritic plaques in AD, tufted astrocytes in progressive supranuclear palsy and astrocytic plaques in corticobasal degeneration. These results support the hypothesis that tau phosphorylation at Ser208 strongly contributes to unique types of tau aggregation and may be a reliable marker for the presence of mature neurofibrillary tangles.

Introduction: Improving flu vaccination rates in the general population is an important and effective strategy toward reducing morbidity, mortality, and the cost of seasonal influenza. In order to optimize immunization strategies, factors associated with decreased vaccination rates need to be explored. The literature suggests that there is a gender difference in the rate of influenza vaccination but is limited to population-based survey studies and also is inconsistent as to which gender has a higher rate of vaccination. The purpose of this study was to evaluate for a gender-based difference in the rate of influenza vaccination among patients who presented for an annual physical examination during the 2018 to 2019 influenza season. Methods: In this multi-site, retrospective chart review, a total of 1193 patients (608 female and 585 male) who underwent an annual physical examination in April of 2019 were included. Baseline medical information was collected, as well as demographic characteristics and influenza vaccination status. The proportion of patients who underwent influenza vaccination was compared between males and females using multivariable logistic regression models; odds ratios (ORs) were estimated. Results: The likelihood of influenza vaccination was significantly higher in females (62.8%) compared to males (53.2%) in both unadjusted analysis (OR = 1.49, P < .001) and in multivariable analysis adjusting for the potential confounding influences of clinic location, BMI, insurance type, and occupation (OR = 1.42, P = .005). Interestingly, a higher influenza vaccination rate for females compared to males was observed in patients age<60 years (OR = 1.70, P = .025) and between ages 60 and 75 (OR = 1.66, P = .009), but not for patients older than 75 years (OR = 1.12, P = .66). Conclusion: Our findings indicate that the rate of influenza vaccination is higher for females than for males who presented for an annual preventive physical exam and who are younger than 75 years old.