1. Synaptic oligomeric tau in Alzheimer's disease - A potential culprit in the spread of tau pathology through the brain.
- Author
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Colom-Cadena M, Davies C, Sirisi S, Lee JE, Simzer EM, Tzioras M, Querol-Vilaseca M, Sánchez-Aced É, Chang YY, Holt K, McGeachan RI, Rose J, Tulloch J, Wilkins L, Smith C, Andrian T, Belbin O, Pujals S, Horrocks MH, Lleó A, and Spires-Jones TL
- Subjects
- Animals, Humans, Mice, Amyloid beta-Peptides metabolism, Brain metabolism, Presynaptic Terminals metabolism, Synapses metabolism, Alzheimer Disease metabolism, Alzheimer Disease pathology, tau Proteins metabolism
- Abstract
In Alzheimer's disease, fibrillar tau pathology accumulates and spreads through the brain and synapses are lost. Evidence from mouse models indicates that tau spreads trans-synaptically from pre- to postsynapses and that oligomeric tau is synaptotoxic, but data on synaptic tau in human brain are scarce. Here we used sub-diffraction-limit microscopy to study synaptic tau accumulation in postmortem temporal and occipital cortices of human Alzheimer's and control donors. Oligomeric tau is present in pre- and postsynaptic terminals, even in areas without abundant fibrillar tau deposition. Furthermore, there is a higher proportion of oligomeric tau compared with phosphorylated or misfolded tau found at synaptic terminals. These data suggest that accumulation of oligomeric tau in synapses is an early event in pathogenesis and that tau pathology may progress through the brain via trans-synaptic spread in human disease. Thus, specifically reducing oligomeric tau at synapses may be a promising therapeutic strategy for Alzheimer's disease., Competing Interests: Declaration of interests T.S.-J. is on the Scientific Advisory Board of Cognition Therapeutics and has received honoraria for talks for industry collaborators. They did not have any involvement in or influence over the current paper. T.S.-J. is also a member of the Neuron Editorial Advisory Board., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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