Synaptic oligomeric tau in Alzheimer's disease - A potential culprit in the spread of tau pathology through the brain
Colom-Cadena, Martí (University of Edinburgh. UK Dementia Research Institute)
Davies, C. (University of Edinburgh. UK Dementia Research Institute)
Sirisi Dolcet, Sonia (Institut d'Investigació Biomèdica Sant Pau)
Lee, J.E. (The University of Edinburgh)
Simzer, E.M. (University of Edinburgh. UK Dementia Research Institute)
Tzioras, M. (University of Edinburgh. UK Dementia Research Institute)
Querol-Vilaseca, Marta (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Sánchez-Aced, Érika (Institut d'Investigació Biomèdica Sant Pau)
Chang, Y.Y. (University of Edinburgh. UK Dementia Research Institute)
Holt, K. (University of Edinburgh. UK Dementia Research Institute)
McGeachan, R.I. (University of Edinburgh. UK Dementia Research Institute)
Rose, J. (University of Edinburgh. UK Dementia Research Institute)
Tulloch, J. (University of Edinburgh. UK Dementia Research Institute)
Wilkins, L. (University of Edinburgh. UK Dementia Research Institute)
Smith, C. (The University of Edinburgh)
Andrian, Teodora (Institut de Bioenginyeria de Catalunya)
Belbin, Olivia (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Pujals, S. (Institut de Química Avançada de Catalunya)
Horrocks, M.H. (The University of Edinburgh)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Spires-Jones, T. L. (University of Edinburgh. UK Dementia Research Institute)
Universitat Autònoma de Barcelona

Date:	2023
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alzheimer ; Synapse ; Tau
Published in:	Neuron, Vol. 111 Núm. 14 (19 2023) , p. 2170-2183.e6, ISSN 1097-4199

DOI: 10.1016/j.neuron.2023.04.020
PMID: 37192625

21 p, 7.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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