Nature Communications (Nov 2022)

Enhanced activity of Alzheimer disease-associated variant of protein kinase Cα drives cognitive decline in a mouse model

  • Gema Lordén,
  • Jacob M. Wozniak,
  • Kim Doré,
  • Lara E. Dozier,
  • Chelsea Cates-Gatto,
  • Gentry N. Patrick,
  • David J. Gonzalez,
  • Amanda J. Roberts,
  • Rudolph E. Tanzi,
  • Alexandra C. Newton

DOI
https://doi.org/10.1038/s41467-022-34679-7
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 16

Abstract

Read online

Mutations that enhance the activity of protein kinase C alpha (PKCα) are associated with Alzheimer’s Disease. Here, the authors report that the enhanced activity of one variant, PKCα M489V, is sufficient to rewire the brain phosphoproteome, drive synaptic degeneration, and impair cognition in a mouse model.