A Novel Heterozygous Missense Variant in the CIAO1 Gene in a Family with Alzheimer's Disease: The Val67Ile Variant Promotes the Interaction of CIAO1 and Amyloid-β Protein Precursor

J Alzheimers Dis. 2021;84(2):599-605. doi: 10.3233/JAD-210706.

Abstract

Familial dementia is a rare inherited disease involving progressive impairment of memory, thinking, and behavior. We report a novel heterozygous pathogenic variant (c.199G > A, p.Val67Ile) in the CIAO1 gene that appears to be co-segregated with Alzheimer's disease in a Japanese family. Biochemical analysis of CIAO1 protein revealed that the variant increases the interaction of CIAO1 with immature amyloid-β protein precursor (AβPP), but not mature or soluble AβPP, indicating plausible CIAO1 involvement in AβPP processing. Our study indicates that a heterozygous variant in the CIAO1 gene may be closely related to autosomal dominant familial dementia.

Keywords: Alzheimer’s disease; CIAO1; CIAO1 protein; amyloid-β protein precursor processing; cognitive decline; dementia; familial; neurogenetics.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / genetics
  • Amyloid beta-Protein Precursor / genetics*
  • Brain / pathology
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Japan
  • Male
  • Metallochaperones / genetics*
  • Mutation, Missense / genetics*
  • Neuroimaging

Substances

  • Amyloid beta-Protein Precursor
  • CIAO1 protein, human
  • Metallochaperones