Molecular changes in the absence of severe pathology in the pulvinar in dementia with Lewy bodies

Daniel Erskine, Jinhui Ding, Alan J. Thomas, Alice Kaganovich, Ahmad Khundakar, Peter S. Hanson, John‐Paul Taylor, Ian G. McKeith, Johannes Attems, Mark R. Cookson, Christopher Morris

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    Abstract

    Background: Dementia with Lewy bodies is characterized by transient clinical features, including fluctuating cognition and visual hallucinations, implicating dysfunction of cerebral hub regions, such as the pulvinar nuclei of the thalamus. However, the pulvinar is typically only mildly affected by Lewy body pathology in dementia with Lewy bodies, suggesting additional factors may account for its proposed dysfunction. Methods: We conducted a comprehensive analysis of postmortem pulvinar tissue using whole-transcriptome RNA sequencing, protein expression analysis, and histological evaluation. Results: We identified 321 transcripts as significantly different between dementia with Lewy bodies cases and neurologically normal controls, with gene ontology pathway analysis suggesting the enrichment of transcripts related to synapses and positive regulation of immune functioning. At the protein level, proteins related to synaptic efficiency were decreased, and general synaptic markers remained intact. Analysis of glial subpopulations revealed astrogliosis without activated microglia, which was associated with synaptic changes but not neurodegenerative pathology. Discussion: These results indicate that the pulvinar, a region with relatively low Lewy body pathological burden, manifests changes at the molecular level that differ from previous reports in a more severely affected region. We speculate that these alterations result from neurodegenerative changes in regions connected to the pulvinar and likely contribute to a variety of cognitive changes resulting from decreased cortical synchrony in dementia with Lewy bodies.

    Original languageEnglish
    Pages (from-to)982-991
    Number of pages10
    JournalMovement Disorders : official journal of the Movement Disorder Society
    Volume33
    Issue number6
    Early online date23 Mar 2018
    DOIs
    Publication statusE-pub ahead of print - 23 Mar 2018

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    Erskine, D., Ding, J., Thomas, A. J., Kaganovich, A., Khundakar, A., Hanson, P. S., Taylor, JP., McKeith, I. G., Attems, J., Cookson, M. R., & Morris, C. (2018). Molecular changes in the absence of severe pathology in the pulvinar in dementia with Lewy bodies. Movement Disorders : official journal of the Movement Disorder Society, 33(6), 982-991. https://doi.org/10.1002/mds.27333