No abstract

Background Tau pathology is a hallmark of Alzheimer’s disease (AD) and other tauopathies. During disease progression, abnormally phosphorylated forms of tau aggregate and accumulate into neurofibrillary tangles, leading to synapse loss, neuroinflammation, and neurodegeneration. Thus, targeting of tau pathology is expected to be a promising strategy for AD treatment. Methods The effect of rutin on tau aggregation was detected by thioflavin T fluorescence and transmission electron microscope imaging. The effect of rutin on tau oligomer-induced cytotoxicity was assessed by MTT assay. The effect of rutin on tau oligomer-mediated the production of IL-1β and TNF-α in vitro was measured by ELISA. The uptake of extracellular tau by microglia was determined by immunocytochemistry. Six-month-old male Tau-P301S mice were treated with rutin or vehicle by oral administration daily for 30 days. The cognitive performance was determined using the Morris water maze test, Y-maze test, and novel object recognition test. The levels of pathological tau, gliosis, NF-kB activation, proinflammatory cytokines such as IL-1β and TNF-α, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunolabeling, immunoblotting, or ELISA. Results We showed that rutin, a natural flavonoid glycoside, inhibited tau aggregation and tau oligomer-induced cytotoxicity, lowered the production of proinflammatory cytokines, protected neuronal morphology from toxic tau oligomers, and promoted microglial uptake of extracellular tau oligomers in vitro. When applied to Tau-P301S mouse model of tauopathy, rutin reduced pathological tau levels, regulated tau hyperphosphorylation by increasing PP2A level, suppressed gliosis and neuroinflammation by downregulating NF-kB pathway, prevented microglial synapse engulfment, and rescued synapse loss in mouse brains, resulting in a significant improvement of cognition. Conclusion In combination with the previously reported therapeutic effects of rutin on Aβ pathology, rutin is a promising drug candidate for AD treatment based its combinatorial targeting of tau and Aβ.

Primary biological aerosol particles (PBAP) such as pollen, fungal spores, bacteria, and viruses represent a major subset of particulate matter for both coarse and fine aerosols. Although PBAP affect climate and human health, there still remains a large uncertainty regarding their sources and characteristics, especially in urban atmospheres. Here we combined online fluorescent biological aerosol particle measurements and offline fluorescent and biomarker analysis in winter in Beijing, a city suffering from severe air pollution. Our results show that the abundance of fluorescent biological particles was higher than that of many other natural environments. Bioaerosol loadings were greatly enhanced during mealtime, indicating local emissions of bioaerosols from human activities. The contributions of fungal spores to total organic carbon (OC) from fluorescent bioaerosol analyses were estimated to be around 10% both in clean and polluted periods. This study highlights the importance of human activities to emit bioaerosols into the atmosphere and the potential uncertainties of modeling bioaerosol effects in climate systems.