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Analysis of primary visual cortex in dementia with Lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations

Khundakar, AA; Hanson, PS; Erskine, D; Lax, NZ; Roscamp, J; Karyka, E; Tsefou, E; ... Morris, CM; + view all (2016) Analysis of primary visual cortex in dementia with Lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations. Acta Neuropathologica Communications , 4 , Article 66. 10.1186/s40478-016-0334-3. Green open access

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Abstract

Dementia with Lewy bodies (DLB) patients frequently experience well formed recurrent complex visual hallucinations (RCVH). This is associated with reduced blood flow or hypometabolism on imaging of the primary visual cortex. To understand these associations in DLB we used pathological and biochemical analysis of the primary visual cortex to identify changes that could underpin RCVH. Alpha-synuclein or neurofibrillary tangle pathology in primary visual cortex was essentially absent. Neurone density or volume within the primary visual cortex in DLB was also unchanged using unbiased stereology. Microarray analysis, however, demonstrated changes in neuropeptide gene expression and other markers, indicating altered GABAergic neuronal function. Calcium binding protein and GAD65/67 immunohistochemistry showed preserved interneurone populations indicating possible interneurone dysfunction. This was demonstrated by loss of post synaptic GABA receptor markers including gephyrin, GABARAP, and Kif5A, indicating reduced GABAergic synaptic activity. Glutamatergic neuronal signalling was also altered with vesicular glutamate transporter protein and PSD-95 expression being reduced. Changes to the primary visual cortex in DLB indicate that reduced GABAergic transmission may contribute to RCVH in DLB and treatment using targeted GABAergic modulation or similar approaches using glutamatergic modification may be beneficial.

Type: Article
Title: Analysis of primary visual cortex in dementia with Lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s40478-016-0334-3
Publisher version: http://doi.org/10.1186/s40478-016-0334-3
Language: English
Additional information: © 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Dementia with Lewy bodies, alpha-synuclein, Primary visual cortex, Hallucinations, Alzheimer's disease, TEMPORAL AREAS TE, PARKINSON-DISEASE DEMENTIA, ALZHEIMERS-DISEASE, MACAQUE MONKEYS, SUBCORTICAL CONNECTIONS, DEPENDENT PLASTICITY, ILLUMINA MICROARRAY, BODY DEMENTIAS, BRAIN, PATHOLOGY
UCL classification: UCL
UCL > Provost and Vice Provost Offices > VP: Health
UCL > Provost and Vice Provost Offices > VP: Health > Translational Research Office
URI: https://discovery.ucl.ac.uk/id/eprint/10038439
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