Neocortical tau propagation is a mediator of clinical heterogeneity in Alzheimer's disease.

ABSTRACT: Heterogeneity in progression of clinical dementia obstructs the general therapeutic potential of current treatments for Alzheimer's disease (AD). Though the mechanisms of this heterogeneity remain unclear, the characterization of bioactive tau species and factors that regulate their seeding behavior might give valuable insight as pathological tau is well correlated with cognitive impairment. Here, we conducted an innovative investigation into the molecular basis of widespread, connectivity-based tau propagation that begins in the inferior temporal gyrus (ITG) and spreads to neocortical areas such as the prefrontal cortex (PFC). Biochemical analysis of human postmortem ITG and PFC tissues revealed individual variability in tau seeding, which correlated with cognitive decline, particularly i

SUBMITTER: Chongtham A 

PROVIDER: S-EPMC12501883 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature