Spread of pathological tau proteins through communicating neurons in human Alzheimer's disease

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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 - http://www.scopus.com/inward/record.url?scp=85085538808&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-15701-2

DO - 10.1038/s41467-020-15701-2

M3 - Article

C2 - 32457389

AN - SCOPUS:85085538808

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 2612

ER -