To date, the vast majority of the tau strain studies have been carried out on fibrillar tau aggregates (19, –, 22); however, recent evidence has demonstrated that the small and soluble prefibrillar aggregates, tau oligomers (TauO), are highly toxic due to their strong ability to seed tau misfolding and propagate the pathology seen across different neurodegenerative diseases (23, –, 25). Here, MAPT is linked to neurodegenerative disease.