Faculty, Staff and Student Publications
Publication Date
7-15-2026
Journal
Neuron
DOI
10.1016/j.neuron.2026.03.001
PMID
41956094
PMCID
PMC13347685
PubMedCentral® Posted Date
7-10-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
The spread of tau pathology across the cerebral cortex is closely tied to cognitive decline in Alzheimer's disease (AD). To investigate mechanisms underlying tau spread, we measured bioactivity of tau seeds from inferior temporal gyrus (ITG) and superior frontal gyrus (SFG) synaptosomes in 128 individuals and demonstrated that tau seed bioactivity associates with tau phosphorylation, neurofibrillary tangles (NFTs), and cognitive impairment. Incorporating genotype data from the same individuals within a Mendelian randomization framework showed that tau seeds in ITG induce NFTs locally as well as drive tau seeds and NFTs in SFG. Integrating antemortem functional magnetic resonance imaging data from the same individuals showed that person-specific connectivity modulates the tau seed-NFT relationships. These findings indicate that tau seeds underlie the spread of NFTs both locally and across distal brain regions via individual-specific connectivity.
Keywords
Humans, tau Proteins, Neurofibrillary Tangles, Magnetic Resonance Imaging, Alzheimer Disease, Female, Male, Brain, Temporal Lobe, Phosphorylation, Aged, Cognitive Dysfunction, Neural Pathways
Published Open-Access
yes
Recommended Citation
Weber, Audrey J; Ng, Bernard; Greathouse, Kelsey M; et al., "Tau Seeds Induce Neurofibrillary Tangle Formation Across Brain Regions via Individual-Specific Connectivity" (2026). Faculty, Staff and Student Publications. 885.
https://digitalcommons.library.tmc.edu/uthshis_docs/885
Graphical Abstract