Vendredi 7 février à 11h30
Lieu : Centre Broca Nouvelle-Aquitaine
Tara Spires Jones
Personal Chair of Neurodegeneration
Deputy Director of the Centre for Discovery Brain Sciences
https://www.ed.ac.uk/
Invitée par 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