Discrimination of prion strain targeting in the central nervous system via reactive astrocyte heterogeneity in CD44 expression

Barry Bradford, Christianus Wijaya, Neil Mabbott

Research output: Contribution to conferencePosterpeer-review

Abstract

Prion diseases are fatal, infectious neurodegenerative conditions that affect a variety of mammalian species including humans. Prion infections are the prototypic protein-misfolding neurodegenerative disorder and cause extensive pathology in the central nervous system (CNS), including abnormal accumulations of misfolded host prion protein, spongiform degeneration, neuronal loss and reactive glial responses. Many different prion agent strains exist and these can differ based on disease duration, clinical signs and the targeting and distribution of pathology in distinct brain areas. The CD44 transmembrane glycoprotein is involved in cell-cell interactions, cell adhesion and migration. We identified that CD44 is highly expressed in a subset of reactive astrocytes, as previously observed in Alzheimer’s, Alexander disease and amyotrophic lateral sclerosis (ALS) patients, in regions of the CNS specifically targeted by prions. The distribution of CD44 was compared in brains from a large collection of 15 distinct prion agent strains transmitted to mice of different prion protein (Prnp) genotypes and the pattern of CD44 upregulation observed in the hippocampus in each prion agent strain and host Prnp genotype combination was unique. Together, our data reveal CD44 as a novel marker to detect reactive astrocyte heterogeneity in brain areas targeted during prion disease and for enhanced identification of distinct prion agent strains. These data imply an early and critical role for astrocytes in neuroinflammatory and neurodegenerative responses. The impact upon synapse maintenance and potential targeting for therapeutic interventions are yet to be determined. These findings may also aid in the diagnosis amongst the broad spectrum of human dementias.
Original languageEnglish
Publication statusPublished - 30 Aug 2019
EventScottish Neuroscience Group Meeting 2019 - Herriot Watt University, Edinburgh, United Kingdom
Duration: 30 Aug 2019 → …
https://www.edinburghneuroscience.ed.ac.uk/events/SNG2019

Symposium

SymposiumScottish Neuroscience Group Meeting 2019
Abbreviated titleSNG 2019
Country/TerritoryUnited Kingdom
CityEdinburgh
Period30/08/19 → …
Internet address

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