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Altered synapses and gliotransmission in Alzheimer's disease and AD model mice


Mitew, S and Kirkcaldie, MTK and Dickson, TC and Vickers, JC, Altered synapses and gliotransmission in Alzheimer's disease and AD model mice, Neurobiology of Aging, 34, (10) pp. 2341-2351. ISSN 0197-4580 (2013) [Refereed Article]

Copyright Statement

Copyright 2013 Elsevier

DOI: doi:10.1016/j.neurobiolaging.2013.04.010


Amyloid-β (Aβ) plaque accumulation in Alzheimer's disease (AD) is associated with glutamatergic synapse loss, but less is known about its effect on inhibitory synapses. Here, we demonstrate that vesicular γ-aminobutyric acid (GABA) transporter (VGAT) presynaptic bouton density is unaffected in human preclinical and end-stage AD and in APP/PS1 transgenic (TG) mice. Conversely, excitatory vesicular glutamate transporter 1 (VGlut1) boutons are significantly reduced in end-stage AD cases and less reduced in preclinical AD cases and TGs. Aged TGs also show reduced protein levels of VGlut1 and synaptophysin but not VGAT or glutamate decarboxylase (GAD). These findings indicate that GABAergic synapses are preserved in human AD and mouse TGs. Synaptosomes isolated from plaque-rich TG cortex had significantly higher GAD activity than those from plaque-free cerebellum or the cortex of wild-type littermates. Using tissue fractionation, this increased activity was localized to glial synaptosomes, suggesting that Aβ plaques stimulate increased astrocyte GABA synthesis. © 2013 Elsevier Inc. All rights reserved.

Item Details

Item Type:Refereed Article
Keywords:Excitatory synapse, Inhibitory synapse, Glutamate decarboxylase, Astrocytes, Amyloid plaque, Alzheimer's disease
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Mitew, S (Mr Stanislaw Mitew)
UTAS Author:Kirkcaldie, MTK (Dr Matthew Kirkcaldie)
UTAS Author:Dickson, TC (Professor Tracey Dickson)
UTAS Author:Vickers, JC (Professor James Vickers)
ID Code:85904
Year Published:2013
Web of Science® Times Cited:101
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-08-14
Last Modified:2017-11-06

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