FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease.
Tingxiang YanJingjing LiangJu GaoLuwen WangHisashi Fujiokanull nullXiaofeng ZhuXinglong WangPublished in: Nature communications (2020)
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.
Keyphrases
- mouse model
- binding protein
- protein protein
- amino acid
- poor prognosis
- cerebral ischemia
- multiple sclerosis
- high resolution
- lipopolysaccharide induced
- machine learning
- cognitive impairment
- signaling pathway
- subarachnoid hemorrhage
- resting state
- blood brain barrier
- small molecule
- transcription factor
- gene expression
- mass spectrometry
- functional connectivity
- big data
- long non coding rna
- climate change
- brain injury
- drug induced
- genome wide identification