FAM222A encodes a protein which accumulates in plaques in Alzheimer’s disease
Document Type
Article
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.
Publication Date
12-1-2020
Publication Title
Nature Communications
E-ISSN
20411723
Volume
11
Issue
1
PubMed ID
31964863
Digital Object Identifier (DOI)
10.1038/s41467-019-13962-0
Recommended Citation
Yan, Tingxiang; Liang, Jingjing; Gao, Ju; Wang, Luwen; Fujioka, Hisashi; Weiner, Michael W.; Schuff, Norbert; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Aisen, Paul; Aisen, Paul; Toga, Arthur W.; Jimenez, Gustavo; Donohue, Michael; Gessert, Devon; Harless, Kelly; Salazar, Jennifer; Cabrera, Yuliana; Walter, Sarah; Hergesheimer, Lindsey; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Schneider, Lon S.; Pawluczyk, Sonia; Becerra, Mauricio; Teodoro, Liberty; and Spann, Bryan M., "FAM222A encodes a protein which accumulates in plaques in Alzheimer’s disease" (2020). Neurology. 663.
https://scholar.barrowneuro.org/neurology/663