TY - JOUR
T1 - Spread of pathological tau proteins through communicating neurons in human Alzheimer's disease
AU - Vogel, Jacob W.
AU - Iturria-Medina, Yasser
AU - Strandberg, Olof T.
AU - Smith, Ruben
AU - Levitis, Elizabeth
AU - Evans, Alan C.
AU - Hansson, Oskar
AU - Alzheimer's Disease Neuroimaging Initiative
AU - Swedish BioFinder Study
A2 - Lätt, Jimmy
A2 - Nilsson, Markus
A2 - Ståhlberg, Freddy
A2 - Maly Sundgren, Pia
A2 - van Westen, Danielle
A2 - Jögi, Jonas
A2 - Hägerström, Douglas
A2 - Olsson, Tomas G
A2 - Wollmer, Per
PY - 2020/5/26
Y1 - 2020/5/26
N2 - Tau is a hallmark pathology of Alzheimer's disease, and animal models have suggested that tau spreads from cell to cell through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) to simulate tau spread, and compare these simulations to observed patterns measured using tau-PET in 312 individuals along Alzheimer's disease continuum. Up to 70% of the variance in the overall spatial pattern of tau can be explained by our model. Surprisingly, the ESM predicts the spatial patterns of tau irrespective of whether brain Aβ is present, but regions with greater Aβ burden show greater tau than predicted by connectivity patterns, suggesting a role of Aβ in accelerating tau spread. Altogether, our results provide evidence in humans that tau spreads through neuronal communication pathways even in normal aging, and that this process is accelerated by the presence of brain Aβ.
AB - Tau is a hallmark pathology of Alzheimer's disease, and animal models have suggested that tau spreads from cell to cell through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) to simulate tau spread, and compare these simulations to observed patterns measured using tau-PET in 312 individuals along Alzheimer's disease continuum. Up to 70% of the variance in the overall spatial pattern of tau can be explained by our model. Surprisingly, the ESM predicts the spatial patterns of tau irrespective of whether brain Aβ is present, but regions with greater Aβ burden show greater tau than predicted by connectivity patterns, suggesting a role of Aβ in accelerating tau spread. Altogether, our results provide evidence in humans that tau spreads through neuronal communication pathways even in normal aging, and that this process is accelerated by the presence of brain Aβ.
UR - https://www.nature.com/articles/s41467-021-25193-3
U2 - 10.1038/s41467-020-15701-2
DO - 10.1038/s41467-020-15701-2
M3 - Article
C2 - 32457389
AN - SCOPUS:85085538808
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
M1 - 2612
ER -
