Amyloid-β in Alzheimer's disease - front and centre after all?

The amyloid hypothesis, which proposes that accumulation of the peptide amyloid-β at synapses is the key driver of Alzheimer's disease (AD) pathogenesis, has been the dominant idea in the field of Alzheimer's research for nearly 30 years. Recently, however, serious doubts about its validity have emerged, largely motivated by disappointing results from anti-amyloid therapeutics in clinical trials. As a result, much of the AD research effort has shifted to understanding the roles of a variety of other entities implicated in pathogenesis, such as microglia, astrocytes, apolipoprotein E and several others.

Nafamostat reduces systemic inflammation in TLR7-mediated virus-like illness.

Background: The serine protease inhibitor nafamostat has been proposed as a treatment for COVID-19, by inhibiting TMPRSS2-mediated viral cell entry. Nafamostat has been shown to have other, immunomodulatory effects, which may be beneficial for treatment, however animal models of ssRNA virus infection are lacking. In this study, we examined the potential of the dual TLR7/8 agonist R848 to mimic the host response to an ssRNA virus infection and the associated behavioural response.