Insights into Novel Therapies and the Pathogenesis of Alzheimer's disease, and the Possible Role of COVID-19

Abstract

The Wisniewski laboratory has helped develop novel biomarkers and therapeutic approaches to AD, particular immunotherapeutic approaches that affect both the adaptive and innate immune systems. We have developed a means to stimulate innate immunity to ameliorate AD pathology, which we have tested in aged squirrel monkeys, and now are conducting a phase I clinical trial. We have also developed both active and passive immunization that specifically targets the dominant β-sheet secondary structure of multiple toxic oligomers concurrently (including both Aβ and tau oligomers). Recently we have also documented the neurological manifestations of SARS-CoV-2 infection (in particular cognitive dysfunction) and associated biomarkers of neurodegeneration and neuroinflammation. We have also developed an unbiased proteomic methodology that produces robust data utilizing archival formalin, fixed paraffin embedded human tissue, using this method to perform the most extensive proteomic analysis of amyloid plaques and the phosphorylated tau interaction, as well as to characterize the amyloid proteome of distinct subtypes of AD including rapidly progressive AD and AD in Down syndrome. These studies have helped enhance the understanding of the pathogenesis of AD, and also with the development of novel therapies.