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.

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.

• Authors: Haitian Nan, Yeon-Jeong Kim, Mai Tsuchiya, Toko Fukao, Noriko Hara, Atsushi Hagihara, Kenya Nishioka, Nobutaka Hattori, Norikazu Hara, Takeshi Ikeuchi, Toshihisa Ohtsuka, Yoshihisa Takiyama
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 84 Issue 2 Pg. 599-605 ( 2021) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 34569959 (Publication Type: Letter, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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