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

Nat Commun. 2020 Jan 21;11(1):411. doi: 10.1038/s41467-019-13962-0.

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 types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 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

Substances

  • Amyloid beta-Peptides
  • Amyloidogenic Proteins
  • FAM222A protein, human
  • Fam222a protein, mouse
  • Nerve Tissue Proteins