Logo image
Spread of pathological tau proteins through communicating neurons in human Alzheimer's disease
Journal article   Open access   Peer reviewed

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

Jacob W Vogel, Yasser Iturria-Medina, Olof T Strandberg, Ruben Smith, Elizabeth Levitis, Alan C Evans, Oskar Hansson, Alzheimer’s Disease Neuroimaging Initiative and Swedish BioFinder Study
Nature communications, Vol.11(1), pp.2612-2612
05/26/2020
DOI: 10.1038/s41467-020-15701-2
PMCID: PMC7251068
PMID: 32457389
url
https://doi.org/10.1038/s41467-020-15701-2View
Published (Version of record) Open Access

Abstract

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.
Aged Alzheimer Disease - diagnostic imaging Alzheimer Disease - metabolism Alzheimer Disease - pathology Amyloid beta-Peptides - metabolism Brain - diagnostic imaging Brain - metabolism Brain - physiology Cognitive Dysfunction - diagnostic imaging Cognitive Dysfunction - metabolism Cognitive Dysfunction - pathology Connectome Female Humans Male Membrane Proteins - metabolism Models, Neurological Nerve Net - diagnostic imaging Nerve Net - metabolism Nerve Net - pathology Positron-Emission Tomography

Details

Logo image