Molecular mechanisms mediating the prion-like propagation of tau aggregates between neurons and across brain regions in tau-related dementias
ARTICLE ONGOING UPDATE
K. M. Nady
Sharkya STEM School, Zagazig, Egypt
Publication date: July 10, 2026
Sharkya STEM School, Zagazig, Egypt
Publication date: July 10, 2026
DOI: http://doi.org/10.34614/JIYRC2026I630
ABSTRACT
Tau aggregation and neurofibrillary tangle formation are defining features of tau-related dementias and follow stereotyped anatomical progression from the entorhinal cortex to interconnected cortical regions. While intracellular mechanisms of tau misfolding and aggregation are well described, the molecular processes enabling inter-neuronal and circuit-level propagation remain incompletely understood, representing a critical gap in current models of disease progression. This study addresses the research question of which molecular mechanisms mediate the prion-like propagation of tau aggregates between neurons and across brain regions. A structured narrative literature review was conducted to integrate molecular, structural, cellular, and network-level evidence. The analysis supports a multifactorial model in which seed-competent conformational states, strain-related structural properties, activity-regulated release and uptake, receptor-mediated internalization, connectivity-constrained transmission, and cell-type–specific proteostasis capacity collectively shape propagation dynamics. Together, these interacting mechanisms provide an integrated framework explaining how tau pathology extends across vulnerable neural circuits during disease progression.
Tau aggregation and neurofibrillary tangle formation are defining features of tau-related dementias and follow stereotyped anatomical progression from the entorhinal cortex to interconnected cortical regions. While intracellular mechanisms of tau misfolding and aggregation are well described, the molecular processes enabling inter-neuronal and circuit-level propagation remain incompletely understood, representing a critical gap in current models of disease progression. This study addresses the research question of which molecular mechanisms mediate the prion-like propagation of tau aggregates between neurons and across brain regions. A structured narrative literature review was conducted to integrate molecular, structural, cellular, and network-level evidence. The analysis supports a multifactorial model in which seed-competent conformational states, strain-related structural properties, activity-regulated release and uptake, receptor-mediated internalization, connectivity-constrained transmission, and cell-type–specific proteostasis capacity collectively shape propagation dynamics. Together, these interacting mechanisms provide an integrated framework explaining how tau pathology extends across vulnerable neural circuits during disease progression.
