Rakez Kayed, PhD, The University of Texas Medical Branch, Galveston, TX, discusses pathological tau aggregates in human tauopathies. Neurofibrillary tau tangles are a hallmark of Alzheimer’s disease, but research in recent years has also emphasized the role of tau oligomers in disease pathophysiology. Tau oligomers are conformationally distinct from fibrils. They are smaller, hydrophobic, dynamic molecules and have been shown to be more effective than larger insoluble aggregates in the initiation of tau seeding and spread of tau pathology. In a study that extracted pure populations of tau fibrils and oligomers from the Alzheimer’s disease brain, only tau oligomers were shown to propagate abnormal tau conformation of endogenous murine tau. Ongoing work aims to further characterize the role of oligomers in disease initiation and progression in vivo. Confirming atomic structures and designing reliable quantification assays will be important moving forward. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA
