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Record W3002496690 · doi:10.1038/s41467-019-13962-0

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

2020· article· en· W3002496690 on OpenAlexafffund
Tingxiang Yan, Jingjing Liang, Ju Gao, Luwen Wang, Hisashi Fujioka, Michael W. Weiner, Norbert Schuff, Howard J. Rosen, Bruce L. Miller, David C. Perry, Paul Aisen, Arthur W. Toga, Gustavo Jiménez, Michael Donohue, Devon Gessert, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Sarah Walter, Lindsey Hergesheimer, Karen Crawford, Scott Neu, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, Ronald Petersen, Clifford R. Jack, Matt A. Bernstein, Bret Borowski, Jeff Gunter, Matthew L. Senjem, Prashanthi Vemuri, David T. Jones, Kejal Kantarci, Chad Ward, Sara S. Mason, Colleen S. Albers, David S. Knopman, Kris Johnson, Neill R. Graff‐Radford, Francine Parfitt, Kim Poki-Walker, William J. Jagust, Susan Landau, John Q. Trojanowki, Leslie M. Shaw, Jason Karlawish, David A. Wolk, Sanjeev Vaishnavi, Christopher M. Clark, Steven E. Arnold, Virginia Lee, Magdalena Korecka, Michal Figurski, Laurel Beckett, Danielle Harvey, Charles DeCarli, Evan Fletcher, Pauline Maillard, John Olichney, Owen Carmichael, Robert C. Green, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Andrew J. Saykin, Tatiana Foroud, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, John C. Morris, Marc Raichle, David M. Holtzman, Nigel J. Cairns, Erin Franklin, Lisa Taylor‐Reinwald, Beau M. Ances, David Winkfield, Maria Carroll, Angela Oliver, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Lew Kuller, Oscar L. López, MaryAnn Oakley, Donna M. Simpson, Steven M. Paul, Norman Relkin, Gloria Chiang, Michael Z. Lin, Lisa Ravdin, Peter Davies, Marek-Marsel Mesulam, Emily Rogalskı, Kristine Lipowski, Sandra Weıntraub, Borna Bonakdarpour, Diana Kerwin, Chuang‐Kuo Wu, Nancy Johnson, Peter J. Snyder, Tom Montine, Lean Thal, James B. Brewer, Helen Vanderswag, Adam Fleisher, Paul M. Thompson, Ellen Woo, Daniel Silverman, Edmond Teng, Sarah Kremen, Liana G. Apostolova, Kathleen Tingus, Po H. Lu, George Bartzokis, Robert A. Koeppe, Jaimie Ziolkowski, Judith L. Heidebrink, Joanne Lord, Norm Foster, Marilyn Albert, Chiadi U. Onyike, Daniel D’Agostino, Stephanie Kielb, Joseph F. Quinn, Lisa C. Silbert, Betty Lind, Jeffrey Kaye, Raina Carter, Sara Dolen, Javier Villanueva‐Meyer, Valory Pavlik, Nathaniel Pacini, Ashley Lamb, Joseph S. Kass, Rachelle S. Doody, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Randy Yeh, Daniel Marson, David Geldmacher, Marissa Natelson, Randall Griffith, David Clark, John Brockington, Hillel Grossman, Effie Mitsis, Raj C. Shah, Melissa Lamar, Patricia Samuels, Martin Sadowski, Mohammed O. Sheikh, Jamika Singleton-Garvin, Anaztasia Ulysse, Mrunalini Gaikwad, P. Murali Doraiswamy, Olga James, Salvador Borges‐Neto, Terence Z. Wong, Edward Coleman, Charles D. Smith, Gregory A. Jicha, Peter Hardy, Riham El Khouli, Elizabeth Oates, Gary Conrad, Anton P. Porsteinsson, Kim Martin, Nancy Kowalksi, Melanie Keltz, Bonnie S. Goldstein, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Gaby Thai, Aimee Pierce, Beatriz Yáñez‐Rivera, Elizabeth Sosa, Megan Witbracht, Steven Potkin, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Christopher H. van Dyck, Richard E. Carson, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Neil W. Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Ntekim E. Oyonumo, Joanne Allard, Olu Ogunlana, Alan J. Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, Jerome A. Yesavage, Joy L. Taylor, Steven Chao, Barton Lane, Allyson Rosen, Jared Tinklenberg, Douglas W. Scharre, Maria Kataki, Rawan Tarawneh, Earl A. Zimmerman, Dzintra Celmins, David Hart, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Mia Yang, Akiva Mintz, Del D. Miller, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Susan K. Schultz, Amanda Smith, Christi Leach, Balebail Ashok Raj, Kristin Fargher, Eric M. Reiman, Kewei Chen, Pierre N. Tariot, Anna Burke, Joel Hetelle, Kathryn DeMarco, Nadira Trncic, Stephanie Reeder, Edward Zamrini, Christine M. Belden, Sherye A. Sirrel, Ranjan Duara, Maria T. Greig‐Custo, Rosemarie Rodriguez, Charles Bernick, Donna Munic, Zaven S. Khachaturian, Neil Buckholtz, John Hsiao, William Z. Potter, Howard Fillit, Franz Hefti, Carl Sadowsky, Teresa Villena, Ging‐Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, William Pavlosky, Irina Rachinsky, Dick Drost, Sandra E. Black, Bojana Stefanovic, Chrinthaka Heyn, Brian R. Ott, Geoffrey Tremont, Lori A. Daniello, Courtney Bodge, Stephen Salloway, Paul Malloy, Stephen Correia, Athena Lee, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Vernice Bates, Horacio Capote, Michelle Rainka, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, John Rogers, Andrew Kertesz, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Smita Kittur, Michael Borrie, T.-Y. Lee, Robert Bartha, Richard Frank, Nick C. Fox, Veronika Logovinsky, Maria Corrillo, Greg Sorensen, Xiaofeng Zhu, Xinglong Wang

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsSunnybrook Health Science CentreSt Joseph's Health CareSt Joseph's Health CentreMcGill UniversityJewish General Hospital
FundersNational Human Genome Research InstituteNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchGenentechIXICOH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationPfizerBiogenBioClinicaF. Hoffmann-La RocheUniversity of Southern CaliforniaNovartis Pharmaceuticals CorporationU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbAlzheimer's Disease Neuroimaging InitiativeNational Center for Advancing Translational SciencesMeso Scale DiagnosticsNational Institute on AgingAlzheimer's AssociationNational Institutes of HealthU.S. Department of Health and Human ServicesFoundation for the National Institutes of Health
KeywordsNeuroinflammationAtrophyPhenotypeAmyloid precursor proteinAmyloid (mycology)NeuroscienceAlzheimer's diseaseBiologyPathologyDiseaseMedicineGeneGenetics

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0030.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.083
GPT teacher head0.392
Teacher spread0.309 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations33
Published2020
Admission routes2
Has abstractyes

Explore more

Same venueNature Communications→Same topicAlzheimer's disease research and treatments→French-language works237,207→