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

journal contribution
posted on 2023-05-17, 19:01 authored by Mitew, S, Matthew KirkcaldieMatthew Kirkcaldie, Tracey DicksonTracey Dickson, James VickersJames Vickers
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.

History

Publication title

Neurobiology of Aging

Volume

34

Issue

10

Pagination

2341-2351

ISSN

0197-4580

Department/School

Tasmanian School of Medicine

Publisher

Elsevier Science Inc

Place of publication

360 Park Ave South, New York, USA, Ny, 10010-1710

Rights statement

Copyright 2013 Elsevier

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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