The AD/ADRD Interdisciplinary Research Network on Biologically Active Tau Aggregate Polymorphs from Alzheimer’s Disease and Related Dementias

Abstract

AbstractBackgroundTauopathies, including Alzheimer’s disease (AD), are characterized by intracellular lesions composed of aggregated and post‐translationally modified tau proteins. Methods for preparation and biochemical characterization of stable filaments from various tauopathies are well established. In contrast, methods for preparation of soluble oligomeric tau aggregates have not been standardized to the same degree. Additionally, the structures of oligomers which associate most closely with disease propagation and toxicity, are not fully established. The AD/ADRD Resource Network aims to isolate structurally vetted tau filaments and oligomers from human tauopathy cases and distribute them to the research community. In addition, it seeks to bank and distribute detection reagents and associated protocols. The overall mission of the network is to support impactful tauopathy research.MethodTauopathies, including Alzheimer’s disease (AD), are characterized by intracellular lesions composed of aggregated and post‐translationally modified tau proteins. Methods for preparation and biochemical characterization of stable filaments from various tauopathies are well established. In contrast, methods for preparation of soluble oligomeric tau aggregates have not been standardized to the same degree. Additionally, the structures of oligomers which associate most closely with disease propagation and toxicity, are not fully established. The AD/ADRD Resource Network aims to isolate structurally vetted tau filaments and oligomers from human tauopathy cases and distribute them to the research community. In addition, it seeks to bank and distribute detection reagents and associated protocols. The overall mission of the network is to support impactful tauopathy research.ResultProtocols for simultaneous isolation of oligomeric and filamentous tau aggregates have been developed along with analytical and quantitative methods to estimate sample heterogenicity and stability. Resource Network members are establishing cross‐laboratory analytical benchmarks for experiments to ensure rigor and reproducibility of results.ConclusionThe AD/ADRD Research Network banks rigorously validated preparations of structurally vetted tau aggregates along with directed protocols and reagents. Dissemination of these reagents is expected to maximize rigor and reproducibility of basic research involving tau protein aggregates.