Amplification, not spreading limits rate of tau aggregate accumulation in Alzheimer's disease
Meisl, G.; Zuo, Y.; Allinson, K.; Rittman, T.; DeVos, S.; Sanchez, J. S.; Xu, C. K.; Duff, K. E.; Johnson, K. A.; Rowe, J.; Hyman, B.; Knowles, T. P.; Klenerman, D.
Show abstract
Both the replication of protein aggregates and their spreading throughout the brain are implicated in the progression of Alzheimers disease (AD). However, the rates of these processes are unknown and the identity of the rate-determining process in humans has therefore remained elusive. By bringing together chemical kinetics with measurements of tau seeds and aggregates across brain regions, we are able to quantify their replication rate in human brains. Remarkably, we obtain comparable rates in several different datasets, with 5 different methods of tau quantification, from seed amplification assays in vitro to tau PET studies in living patients. Our results suggest that the overall rate of accumulation of tau in neocortical regions is limited not by spreading between brain regions but by local replication, which doubles the number of seeds every ~5 years. Thus, we propose that limiting local replication constitutes the most promising strategy to control tau accumulation during AD.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.