Why do some people with AD slide rapidly into severe dementia, while others decline gradually over more than a decade? Part of the answer could come down to which biochemical forms of tau inhabit a person’s brain, suggests a study published June 22 in Nature Medicine. Among postmortem brain samples from people with advanced AD, Bradley Hyman at Massachusetts General Hospital in Charlestown and colleagues found a striking variability in tau’s ability to seed aggregation. The scientists tied aggregation-prone forms of tau in the postmortem brain to a more rapid course of disease during life. They pegged large, soluble tau oligomers—phosphorylated on specific residues—as the most hazardous species. Antibodies trained against these types of tau stopped its aggregation. The findings cast tau’s behavior as a major prognostic determinant for AD, and support the concept of targeting these troublesome forms of the protein with therapeutics.
- Tau seeding activity varied by an order of magnitude among 32 people with AD.
- Seeding activity, hyperphosphorylation, and oligomerization of tau correlated with clinical aggressiveness.
- Phosphorylation of specific tau residues associated with rate of decline.
“This is a well-designed study underlining once more the importance of the soluble tau oligomeric assemblies over long tau filaments in Alzheimer’s disease, as well as heterogeneity in tau oligomers,” commented Rakez Kayed of the University of Texas Medical Branch in Galveston.
Read the full findings in this article on the Alz Forum website – https://www.alzforum.org/news/research-news/tau-why-alzheimers-worsens-fast-some-slowly-others