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Monthly conference (PhD seminar series) – Tara Spires Jones

Friday 7 February 2020 / 11:30

Unravelling the role of synapse degeneration in Alzheimer's disease

Venue : Centre Broca Nouvelle-Aquitaine

Tara Spire Jones
Tara Spire Jones

Tara Spire Jones
Personal Chair of Neurodegeneration
Deputy Director of the Centre for Discovery Brain Sciences
https://www.ed.ac.uk/

Invited by Bordeaux Neurocampus et la NBA

Abstract

Synapse loss correlates strongly with cognitive decline in Alzheimer’s disease, but the mechanisms underpinning this phenomenon remain unclear. In our group, we have evidence from mouse models and human post mortem brain tissue implicating pathological proteins in synapse degeneration mediated by interactions between neurons and glia. In a transgenic mouse model of Alzheimer’s disease, behavioural changes are accompanied by accumulation of amyloid beta and tau in synapses, increases in inflammatory gene expression, and phagocytosis of synapses by microglia. When soluble tau levels were lowered, tau in synapses was reduced and the behavioural phenotype and inflammatory gene expression changes recovered. In human AD brain, we observe similar accumulations of pathological amyloid beta and tau in synapses, increases in proteins involved in microglial inflammation, and increased microglial ingestion of synaptic proteins compared to control brain. Together, our data implicate pathological protein accumulation in synapses may contribute to synapse phagocytosis by microglia.

Selected Publications

Tzioras M, Daniels MJD, King D, Popovic K, Holloway RK, Stevenson AJ, Tulloch J, Kandasamy J, Sokol D, Latta C, Rose J, Smith C, Miron VE, HEnstridge CM, McColl BW, Spires-Jones TL (2019) Altered synaptic ingestion by human microglia in Alzheimer’s disease. bioRxiv  https://doi.org/10.1101/795930

Pickett EK, Herrmann AG, McQueen J, Abt K, Dando O, Tulloch J, Jain P, Dunnett S, Sohrabi S, Fjeldstad MP, Calkin W, Murison L, Jackson RJ, Tzioras M, Stevenson A, d’Orange M, Hooley M, Davies C, Colom-Cadena M, Anton-Fernandez A, King D, Oren I, Rose J, McKenzie CA, Allison E, Smith C, Hardt O, Henstridge CM, Hardingham GE, Spires-Jones TL (2019) Amyloid Beta and Tau Cooperate to Cause Reversible Behavioral and Transcriptional Deficits in a Model of Alzheimer’s Disease. Cell Rep 29: 3592-3604 e3595 Doi 10.1016/j.celrep.2019.11.044;

Jackson RJ, Rose J, Tulloch J, Henstridge C, Smith C, Spires-Jones TL (2019) Clusterin accumulates in synapses in Alzheimer’s disease and is increased in apolipoprotein E4 carriers. Brain Commun 1: fcz003 Doi 10.1093/braincomms/fcz003;

Hesse R, Hurtado ML, Jackson RJ, Eaton SL, Herrmann AG, Colom-Cadena M, Tzioras M, King D, Rose J, Tulloch J, McKenzie CA, Smith C, Henstridge CM, Lamont D, Wishart TM, Spires-Jones TL (2019) Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype. Acta Neuropathol Commun 7: 214 Doi 10.1186/s40478-019-0847-7;

Henstridge CM, Hyman BT, Spires-Jones TL (2019) Beyond the neuron-cellular interactions early in Alzheimer disease pathogenesis. Nat Rev Neurosci 20: 94-108 Doi 10.1038/s41583-018-0113-1

About the speaker

Professor Tara Spires-Jones, DPhil
UK Dementia Research Institute Programme Lead
Deputy Director, Centre for Discovery Brain Sciences
The University of Edinburgh
Founding Editor Brain Communications
Section Editor European Journal of Neuroscience
Board of Reviewing Editors Science
Editorial Board Member Cell Reports

 

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Details

Date:
Friday 7 February 2020
Time:
11:30
Event Categories:
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