GJA1 (connexin43) is a key regulator of Alzheimer’s disease pathogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Yuji Kajiwara, Erming Wang, Minghui Wang, Wun Chey Sin, Kristen J. Brennand, Eric Schadt, Christian C. Naus, Joseph Buxbaum, Bin Zhang

ABSTRACT

GJA1 (connexin43) has been predicted as the top key driver of an astrocyte enriched subnetwork associated with Alzheimer's disease (AD). In this study, we comprehensively examined GJA1 expression across 29 transcriptomic and proteomic datasets from post-mortem AD and normal control brains. We demonstrated that GJA1 was strongly associated with AD amyloid and tau pathologies and cognitive functions. RNA sequencing analysis of Gja1-/- astrocytes validated that Gja1 regulated the subnetwork identified in AD, and many genes involved in Aβ metabolism. Astrocytes lacking Gja1 showed reduced Apoe protein levels as well as impaired Aβ phagocytosis. Consistent with this, wildtype neurons co-cultured with Gja1-/- astrocytes contained higher levels of Aβ species than those with wildtype astrocytes. Moreover, Gja1-/- astrocytes was more neuroprotective under Aβ stress. Our results underscore the importance of GJA1 in AD pathogenesis and its potential for further investigation as a promising pharmacological target in AD. More... »

PAGES

144

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s40478-018-0642-x

    DOI

    http://dx.doi.org/10.1186/s40478-018-0642-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1110826629

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30577786


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