FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31964863.
- Also identified by DOI 10.1038/s41467-019-13962-0 and PMC identifier 6972869.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Alzheimer Disease
- Amyloid beta-Peptides
- Amyloidogenic Proteins
- Cognitive Dysfunction
- Nerve Tissue Proteins
- Plaque, Amyloid
- Protein Aggregation, Pathological