Figure 2.

Selective vulnerability and tau accumulation, seeding, and spreading. Tau pathology follows a set track through the brain in most sporadic AD cases [47,48]. Accumulation of NFTs and soluble tau PTM epitopes typically follow the same path as the disease progresses. In vulnerable neurons, tau PTMs can interfere with tau clearance and lead to tau accumulation. Toxic tau PTMs, like tau truncation, are likely to drive tau export from diseased neurons. Though the mechanisms of tau transfer between neural cells are still being debated, increased abundance in extracellular tau is a hallmark of AD, and toxic tau PTM epitopes may drive the spread of pathology from one brain region to the next.