Synaptic oligomeric tau in Alzheimer's disease — A potential culprit in the spread of tau pathology through the brain
Por:
Colom-Cadena M., Davies C., Sirisi S., Lee J.-E., Simzer E.M., Tzioras M., Querol-Vilaseca M., Sánchez-Aced É., Chang Y.Y., Holt K., McGeachan R.I., Rose J., Tulloch J., Wilkins L., Smith C., Andrian T., Belbin O., Pujals S., Horrocks M.H., Lleó A., Spires-Jones T.L.
Publicada:
15 may 2023
Ahead of Print:
15 may 2023
Resumen:
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.
Filiaciones:
Colom-Cadena M.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
Davies C.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
Sirisi S.:
Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau – Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Lee J.-E.:
EaStCHEM School of Chemistry, The University of Edinburgh, Edinburgh, United Kingdom
IRR Chemistry Hub, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, EH16 4 UU, United Kingdom
Simzer E.M.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
Tzioras M.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
Querol-Vilaseca M.:
Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau – Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Sánchez-Aced É.:
Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau – Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Chang Y.Y.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
Holt K.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
McGeachan R.I.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
Rose J.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
Tulloch J.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
Wilkins L.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
Smith C.:
Centre for Clinical Brain Sciences and Sudden Death Brain Bank, The University of Edinburgh, Edinburgh, United Kingdom
Andrian T.:
Nanoscopy for Nanomedicine Lab, Institute of Bioengineering of Catalonia (IBEC Barcelona Institute of Science and Technology), Barcelona, Spain
Belbin O.:
Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau – Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Pujals S.:
Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain
Horrocks M.H.:
EaStCHEM School of Chemistry, The University of Edinburgh, Edinburgh, United Kingdom
IRR Chemistry Hub, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, EH16 4 UU, United Kingdom
Lleó A.:
Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau – Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Spires-Jones T.L.:
The University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute, Edinburgh, United Kingdom
Green Published, hybrid, Green Submitted, All Open Access, Hybrid Gold, Green
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