. Spread of pathological tau proteins through communicating neurons in human Alzheimer's disease. Nat Commun. 2020 May 26;11(1):2612. PubMed.


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  1. This is another valuable study adding to the growing body of work implicating brain networks in the pathophysiologic mechanisms of Alzheimer’s disease (AD). This is a very important line of investigation that has implications for prevention, treatment, and monitoring AD.

    There are several prominent theories as to how brain networks are involved in the pathogenesis of AD. Reductionist models begin with molecular pathology and some microscale spreading shaped by neuronal connections in various ways. Complex systems models, such as the cascading network failure model, recast neural networks as active players in the pathophysiology that both leads and responds to protein misfolding. Mathematical models on average connectivity matrices from control populations, like the ones used in this study, cannot differentiate these models, and future work should focus on longitudinal multimodal neuroimaging studies that include measures of brain networks in the same group of individuals that are imaged with amyloid- and tau-PET. These studies should test explicit predictions made by these models regarding the relationship between amyloid, tau, and brain networks across the disease continuum.

    View all comments by David Jones
  2. These are exciting findings. It has been suggested previously that tau pathology begins in locus coeruleus, from which it spreads in a connectome‐dependent pattern during the progression of Alzheimer's from the subclinical to clinically overt stages of the disease. It therefore will be both interesting and important to extend these observations to future investigations looking at the spread of tauopathy from the locus coeruleus to the hippocampus.


    . Roles of tau pathology in the locus coeruleus (LC) in age-associated pathophysiology and Alzheimer's disease pathogenesis: Potential strategies to protect the LC against aging. Brain Res. 2017 Dec 21; PubMed.

    . Early alteration of the locus coeruleus in phenotypic variants of Alzheimer's disease. Ann Clin Transl Neurol. 2019 Jul;6(7):1345-1351. Epub 2019 Jun 23 PubMed.

    View all comments by Marcia Ratner

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