FAM222A encodes a protein which accumulates in plaques in Alzheimer’s disease
Authors: Yan Tingxiang , Liang Jingjing , Gao Ju , Wang Luwen , Fujioka Hisashi ,   The Alzheimer Disease Neuroimaging Initiative, Weiner Michael W. , Schuff Norbert , Rosen Howard J. , Miller Bruce L. , Perry David , Aisen Paul , Toga Arthur W. , Jimenez Gustavo , Donohue Michael , Gessert Devon , Harless Kelly , Salazar Jennifer , Cabrera Yuliana , Walter Sarah , Hergesheimer Lindsey , Toga Arthur W. , Crawford Karen , Neu Scott , Schneider Lon S. , Pawluczyk Sonia , Becerra Mauricio , Teodoro Liberty , Spann Bryan M. , Aisen Paul , Petersen Ronald , Jack Clifford R. , Bernstein Matthew , Borowski Bret , Gunter Jeff , Senjem Matt , Vemuri Prashanthi , Jones David , Kantarci Kejal , Ward Chad , Mason Sara S. , Albers Colleen S. , Knopman David , Johnson Kris , Graff-Radford Neill R. , Parfitt Francine , Poki-Walker Kim , Jagust William , Landau Susan , Trojanowki John Q. , Shaw Leslie M. , Karlawish Jason H. , Wolk David A. , Vaishnavi Sanjeev , Clark Christopher M. , Arnold Steven E. , Lee Virginia , Korecka Magdalena , Figurski Michal , Beckett Laurel , Harvey Danielle , DeCArli Charles , Fletcher Evan , Maillard Pauline , Olichney John , Carmichael Owen , Green Robert C. , Sperling Reisa A. , Johnson Keith A. , Marshall Gad A. , Saykin Andrew J. , Foroud Tatiana M. , Shen Li , Faber Kelley , Kim Sungeun , Nho Kwangsik , Farlow Martin R. , Hake Ann Marie , Matthews Brandy R. , Brosch Jared R. , Herring Scott , Morris John , Raichle Marc , Holtzman David , Morris John C. , Cairns Nigel J. , Franklin Erin , Taylor-Reinwald Lisa , Ances Beau , Winkfield David , Carroll Maria , Oliver Angela , Creech Mary L. , Mintun Mark A. , Schneider Stacy , Kuller Lew , Mathis Chet , Lopez Oscar L. , Oakley MaryAnn , Simpson Donna M. , Paul Steven , Relkin Norman , Chiang Gloria , Lin Michael , Ravdin Lisa , Davies Peter , Mesulam M. Marcel , Mesulam Marek-Marsel , Rogalski Emily , Lipowski Kristine , Weintraub Sandra , Bonakdarpour Borna , Kerwin Diana , Wu Chuang-Kuo , Johnson Nancy , Snyder Peter J. , Montine Tom , Donohue Michael , Thal Lean , Brewer James , Vanderswag Helen , Fleisher Adam , Thompson Paul , Woo Ellen , Silverman Daniel H. S. , Teng Edmond , Kremen Sarah , Apostolova Liana , Tingus Kathleen , Lu Po H. , Bartzokis George , Koeppe Robert A. , Ziolkowski Jaimie , Heidebrink Judith L. , Lord Joanne L. , Foster Norm , Albert Marilyn , Onyike Chiadi , D’Agostino Daniel , Kielb Stephanie , Quinn Joseph , Silbert Lisa C. , Lind Betty , Kaye Jeffrey A. , Carter Raina , Dolen Sara , Villanueva-Meyer Javier , Pavlik Valory , Pacini Nathaniel , Lamb Ashley , Kass Joseph S. , Doody Rachelle S. , Shibley Victoria , Chowdhury Munir , Rountree Susan , Dang Mimi , Stern Yaakov , Honig Lawrence S. , Bell Karen L. , Yeh Randy , Marson Daniel , Geldmacher David , Natelson Marissa , Griffith Randall , Clark David , Brockington John , Grossman Hillel , Mitsis Effie , Shah Raj C. , Lamar Melissa , Samuels Patricia , Sadowski Martin , Sheikh Mohammed O. , Singleton-Garvin Jamika , Ulysse Anaztasia , Gaikwad Mrunalini , Doraiswamy P. Murali , James Olga , Borges-Neto Salvador , Wong Terence Z. , Coleman Edward , Smith Charles D. , Jicha Greg , Hardy Peter , El Khouli Riham , Oates Elizabeth , Conrad Gary , Porsteinsson Anton P. , Martin Kim , Kowalksi Nancy , Keltz Melanie , Goldstein Bonnie S. , Makino Kelly M. , Ismail M. Saleem , Brand Connie , Thai Gaby , Pierce Aimee , Yanez Beatriz , Sosa Elizabeth , Witbracht Megan , Potkin Steven , Womack Kyle , Mathews Dana , Quiceno Mary , Levey Allan I. , Lah James J. , Cellar Janet S. , Burns Jeffrey M. , Swerdlow Russell H. , Brooks William M. , van Dyck Christopher H. , Carson Richard E. , Varma Pradeep , Chertkow Howard , Bergman Howard , Hosein Chris , Turner Raymond Scott , Johnson Kathleen , Reynolds Brigid , Kowall Neil , Killiany Ronald , Budson Andrew E. , Norbash Alexander , Johnson Patricia Lynn , Obisesan Thomas O. , Oyonumo Ntekim E. , Allard Joanne , Ogunlana Olu , Lerner Alan , Ogrocki Paula , Tatsuoka Curtis , Fatica Parianne , Johnson Sterling , Asthana Sanjay , Carlsson Cynthia M. , Yesavage Jerome , Taylor Joy L. , Chao Steven , Lane Barton , Rosen Allyson , Tinklenberg Jared , Scharre Douglas W. , Kataki Maria , Tarawneh Rawan , Zimmerman Earl A. , Celmins Dzintra , Hart David , Flashman Laura A. , Seltzer Marc , Hynes Mary L. , Santulli Robert B. , Sink Kaycee M. , Yang Mia , Mintz Akiva , Miller Delwyn D. , Smith Karen Ekstam , Koleva Hristina , Nam Ki Won , Shim Hyungsub , Schultz Susan K. , Smith Amanda , Leach Christi , Raj Balebail Ashok , Fargher Kristin , Reiman Eric M. , Chen Kewei , Tariot Pierre , Burke Anna , Hetelle Joel , DeMarco Kathryn , Trncic Nadira , Fleisher Adam , Reeder Stephanie , Zamrini Edward , Belden Christine M. , Sirrel Sherye A. , Duara Ranjan , Greig-Custo Maria T. , Rodriguez Rosemarie , Bernick Charles , Munic Donna , Khachaturian Zaven , Buckholtz Neil , Hsiao John , Potter William , Fillit Howard , Hefti Franz , Sadowsky Carl , Villena Teresa , Hsiung Ging-Yuek Robin , Mudge Benita , Sossi Vesna , Feldman Howard , Assaly Michele , Finger Elizabeth , Pasternack Stephen , Pavlosky William , Rachinsky Irina , Drost Dick , Kertesz Andrew , Black Sandra , Stefanovic Bojana , Heyn Chrinthaka , Ott Brian R. , Tremont Geoffrey , Daniello Lori A. , Bodge Courtney , Salloway Stephen , Malloy Paul , Correia Stephen , Lee Athena , Pearlson Godfrey D. , Blank Karen , Anderson Karen , Bates Vernice , Capote Horacio , Rainka Michelle , Mintzer Jacobo , Spicer Kenneth , Bachman David , Finger Elizabeth , Pasternak Stephen , Rachinsky Irina , Rogers John , Kertesz Andrew , Drost Dick , Finger Elizabeth , Pasternak Stephen , Rachinsky Irina , Rogers John , Kertesz Andrew , Drost Dick , Pomara Nunzio , Hernando Raymundo , Sarrael Antero , Kittur Smita , Borrie Michael , Lee T.-Y. , Bartha Rob , Frank Richard , Fox Nick , Logovinsky Veronika , Corrillo Maria , Sorensen Greg , Zhu Xiaofeng , Wang Xinglong 
Published: January 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.