TY - JOUR
T1 - FAM222A encodes a protein which accumulates in plaques in Alzheimer’s disease
AU - Yan, Tingxiang
AU - Liang, Jingjing
AU - Gao, Ju
AU - Wang, Luwen
AU - Fujioka, Hisashi
AU - Weiner, Michael W.
AU - Schuff, Norbert
AU - Rosen, Howard J.
AU - Miller, Bruce L.
AU - Perry, David
AU - Aisen, Paul
AU - Toga, Arthur W.
AU - Jimenez, Gustavo
AU - Donohue, Michael
AU - Gessert, Devon
AU - Harless, Kelly
AU - Salazar, Jennifer
AU - Cabrera, Yuliana
AU - Walter, Sarah
AU - Hergesheimer, Lindsey
AU - Toga, Arthur W.
AU - Crawford, Karen
AU - Neu, Scott
AU - Schneider, Lon S.
AU - Pawluczyk, Sonia
AU - Becerra, Mauricio
AU - Teodoro, Liberty
AU - Spann, Bryan M.
AU - Aisen, Paul
AU - Petersen, Ronald
AU - Jack, Clifford R.
AU - Bernstein, Matthew
AU - Borowski, Bret
AU - Gunter, Jeff
AU - Senjem, Matt
AU - Vemuri, Prashanthi
AU - Jones, David
AU - Kantarci, Kejal
AU - Ward, Chad
AU - Mason, Sara S.
AU - Albers, Colleen S.
AU - Knopman, David
AU - Johnson, Kris
AU - Graff-Radford, Neill R.
AU - Parfitt, Francine
AU - Poki-Walker, Kim
AU - Jagust, William
AU - Landau, Susan
AU - Trojanowki, John Q.
AU - Jicha, Greg
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-13962-0
DO - 10.1038/s41467-019-13962-0
M3 - Article
C2 - 31964863
AN - SCOPUS:85078187510
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 411
ER -