期刊
ACTA NEUROPATHOLOGICA COMMUNICATIONS
卷 4, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s40478-016-0334-3
关键词
Dementia with Lewy bodies; alpha-synuclein; Primary visual cortex; Hallucinations; Alzheimer's disease
资金
- Alzheimer's Society
- European Union
- Newcastle University Centre for Brain Ageing and Vitality
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Engineering and Physical Sciences Research Council (EPSRC)
- Economic and Social Research Council (ESRC)
- Medical Research Council (MRC), as part of the cross-council Lifelong Health and Wellbeing Initiative [G0700718]
- Wellcome Trust Centre for Mitochondrial Research [906919]
- UK's National Institute for Health Research (NIHR) Biomedical Research Centre for Ageing and Age-related disease
- UK Department of Health
- UK MRC
- Yvonne Mairy Bequest
- Alzheimer's Research Trust through the Brains for Dementia Research Initiative
- NIHR Biomedical Research Centre Grant in Ageing and Health
- NIHR Biomedical Research Unit in Lewy body Dementia
- National Institute for Health Research
- MRC [G0400074, G0502157, G0900652, MR/L016354/1, G1100540] Funding Source: UKRI
- Alzheimer's Society [181] Funding Source: researchfish
- Medical Research Council [G0400074, G0502157, G1100540, MR/L016354/1, G0900652] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10048] Funding Source: researchfish
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.
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