1. FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease.
- Author
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Yan, Tingxiang, Liang, Jingjing, Gao, Ju, Wang, Luwen, Fujioka, Hisashi, The Alzheimer Disease Neuroimaging Initiative, Weiner, Michael W., Schuff, Norbert, Rosen, Howard J., Miller, Bruce L., Perry, David, Aisen, Paul, Toga, Arthur W., Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Harless, Kelly, Salazar, Jennifer, Cabrera, Yuliana, and Walter, Sarah
- Subjects
ALZHEIMER'S disease ,CEREBRAL atrophy ,AMYLOID plaque ,PROTEINS ,PROTEIN expression ,CENTRAL nervous system physiology - Abstract
Alzheimer's disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD. In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer's disease, and functional analysis suggests it interacts with amyloid-beta. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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