Data from several recent investigations are showing that several tau post-translational modifications (PTMs) may be relevant to Alzheimer’s disease pathology. Lea Grinberg, MD, PhD, Weill Institute for Neurosciences and Memory and Aging Center, University of California, San Francisco, CA, discusses studies looking at tau cleavage by caspase-6 as a relevant PTM. Caspase-6 creates a truncated form of tau that is prone to aggregation and using a monoclonal antibody specific to this truncated tau, its presence was studied in the human brain. The results showed that caspase-6 truncated tau is important in Alzheimer’s disease and other tauopathies with 3-repeat tau. Additionally, many neurons with truncated tau did not show phosphorylated changes, suggesting that looking only at tau phosphorylation may not be an accurate measure of disease. This interview took place during the Alzheimer’s Association International Conference (AAIC) 2021.