Alzheimer’s Disease Tau Consortium: Deep Mass Spectrometry Profiling of Tau Aggregates in Alzheimer’s Disease and Other Tauopathies

This proposal details in-depth work to find links between the two major brain changes in Alzheimer’s disease: extracellular clumps of a protein called amyloid beta, and intraneuronal accumulations of another protein called tau. Specifically, we will investigate whether tau accumulations associated with amyloid beta clumps are different in regard to their molecular composition compared with tau accumulations that form independently of amyloid beta clumps. The question has been partly addressed with older and less sensitive and specific methodology, but never in the detail we are proposing here. We believe this work is essential to improve our understanding of why tau accumulations develop in neurodegenerative dementias, and the work should give clues on novel biomarkers and therapeutics.