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

doi:10.1038/s41467-019-13962-0

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

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Resumen

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.

Idioma original	English
Número de artículo	411
Publicación	Nature Communications
Volumen	11
N.º	1
DOI	https://doi.org/10.1038/s41467-019-13962-0
Estado	Published - dic 1 2020

Nota bibliográfica

Publisher Copyright:
© 2020, The Author(s).

Financiación

This work is supported by grants from the US National Institutes of Health (RF1AG056320 to X.W.) and the US Alzheimer’s Association (AARG-17–499682 to X.W.). Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12–2–0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cog-state; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neu-rotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The

Financiadores	Número del financiador
National Institutes of Health (NIH)
National Institute on Aging	RF1AG056320, U01AG024904, P30AG062715
Alzheimer's Association	ARG-17-499682
National Human Genome Research Institute	R01HG003054
National Center for Advancing Translational Sciences (NCATS)	UL1TR002369

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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10.1038/s41467-019-13962-0

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title = "FAM222A encodes a protein which accumulates in plaques in Alzheimer{\textquoteright}s disease",

abstract = "Alzheimer{\textquoteright}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.",

author = "Tingxiang Yan and Jingjing Liang and Ju Gao and Luwen Wang and Hisashi Fujioka and Weiner, \{Michael W.\} and Norbert Schuff and Rosen, \{Howard J.\} and Miller, \{Bruce L.\} and David Perry and Paul Aisen and Toga, \{Arthur W.\} and Gustavo Jimenez and Michael Donohue and Devon Gessert and Kelly Harless and Jennifer Salazar and Yuliana Cabrera and Sarah Walter and Lindsey Hergesheimer and Toga, \{Arthur W.\} and Karen Crawford and Scott Neu and Schneider, \{Lon S.\} and Sonia Pawluczyk and Mauricio Becerra and Liberty Teodoro and Spann, \{Bryan M.\} and Paul Aisen and Ronald Petersen and Jack, \{Clifford R.\} and Matthew Bernstein and Bret Borowski and Jeff Gunter and Matt Senjem and Prashanthi Vemuri and David Jones and Kejal Kantarci and Chad Ward and Mason, \{Sara S.\} and Albers, \{Colleen S.\} and David Knopman and Kris Johnson and Graff-Radford, \{Neill R.\} and Francine Parfitt and Kim Poki-Walker and William Jagust and Susan Landau and Trojanowki, \{John Q.\} and Greg Jicha",

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AU - Liang, Jingjing

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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

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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SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

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ER -

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

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

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