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The fate of interneurons, GABAA receptor sub-types and perineuronal nets in Alzheimer’s disease

Ali, Afia; Islam, Anam; Constanti, Andrew; (2023) The fate of interneurons, GABAA receptor sub-types and perineuronal nets in Alzheimer’s disease. Brain Pathology , 33 (1) , Article e13129. 10.1111/bpa.13129. Green open access

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Abstract

Alzheimer's disease (AD) is the most common neurological disease, which is associated with gradual memory loss and correlated with synaptic hyperactivity and abnormal oscillatory rhythmic brain activity that precedes phenotypic alterations and is partly responsible for the spread of the disease pathology. Synaptic hyperactivity is thought to be because of alteration in the homeostasis of phasic and tonic synaptic inhibition, which is orchestrated by the GABAA inhibitory system, encompassing subclasses of interneurons and GABAA receptors, which play a vital role in cognitive functions, including learning and memory. Furthermore, the extracellular matrix, the perineuronal nets (PNNs) which often go unnoticed in considerations of AD pathology, encapsulate the inhibitory cells and neurites in critical brain regions and have recently come under the light for their crucial role in synaptic stabilisation and excitatory-inhibitory balance and when disrupted, serve as a potential trigger for AD-associated synaptic imbalance. Therefore, in this review, we summarise the current understanding of the selective vulnerability of distinct interneuron subtypes, their synaptic and extrasynaptic GABAAR subtypes as well as the changes in PNNs in AD, detailing their contribution to the mechanisms of disease development. We aim to highlight how seemingly unique malfunction in each component of the interneuronal GABA inhibitory system can be tied together to result in critical circuit dysfunction, leading to the irreversible symptomatic damage observed in AD.

Type: Article
Title: The fate of interneurons, GABAA receptor sub-types and perineuronal nets in Alzheimer’s disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/bpa.13129
Publisher version: https://doi.org/10.1111/bpa.13129
Language: English
Additional information: © 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Alzheimer’s disease, GABA, interneurons, neurodegeneration, perineuronal nets, Synaptic
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: https://discovery.ucl.ac.uk/id/eprint/10158471
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