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FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease
Journal article   Open access   Peer reviewed

FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease

Tingxiang Yan, Jingjing Liang, Ju Gao, Luwen Wang, Hisashi Fujioka, Xiaofeng Zhu, Xinglong Wang and Alzheimer Disease Neuroimaging Initiative
Nature communications, Vol.11(1), pp.411-411
01/21/2020
DOI: 10.1038/s41467-019-13962-0
PMCID: PMC6972869
PMID: 31964863
url
https://doi.org/10.1038/s41467-019-13962-0View
Published (Version of record) Open Access

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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.
 Aged Aged, 80 and over Alzheimer Disease - diagnostic imaging Alzheimer Disease - genetics Alzheimer Disease - pathology Amyloid beta-Peptides - metabolism Amyloidogenic Proteins - genetics Amyloidogenic Proteins - metabolism Animals Atrophy - diagnostic imaging Atrophy - genetics Atrophy - pathology Brain - diagnostic imaging Brain - pathology Cognitive Dysfunction - genetics Cognitive Dysfunction - pathology Datasets as Topic Disease Models, Animal Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Mice Mice, Transgenic Middle Aged Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Plaque, Amyloid - genetics Plaque, Amyloid - pathology Polymorphism, Single Nucleotide Protein Aggregation, Pathological - diagnostic imaging Protein Aggregation, Pathological - genetics Protein Aggregation, Pathological - pathology

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