Synaptic oligomeric tau in Alzheimer's disease — A potential culprit in the spread of tau pathology through the brain

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 ar...

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Detalles Bibliográficos
Autores: Colom-Cadena, Martí, Davies, Caitlin, Sirisi, Sònia, Lee, Ji Eun, Simzer, Elizabeth M., Tzioras, Makis, Querol-Vilaseca, Marta, Sánchez-Aced, Érika, Chang, Ya Yin, Holt, Kristjan, McGeachan, Robert I., Rose, Jamie, Tulloch, Jane, Wilkins, Lewis, Smith, Colin, Andrian, Teodora, Belbin, Olivia, Pujals, Sílvia, Horrocks, Mathew H., Lleó, Alberto, Spires-Jones, Tara L.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/360922
Acceso en línea:http://hdl.handle.net/10261/360922
https://api.elsevier.com/content/abstract/scopus_id/85160328355
Access Level:acceso abierto
Palabra clave:Tau
Alzheimer
Synapse
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Descripción
Sumario: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.

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