Correlation between Alzheimer’s disease and type 2 diabetes using non-negative matrix factorization
Authors: Chung Yeonwoo , Lee Hyunju ,   the Alzheimer’s Disease Neuroimaging Initiative, Weiner Michael W. , Aisen Paul , Petersen Ronald , Jack Cliford R. , Jagust William , Trojanowki John Q. , Toga Arthur W. , Beckett Laurel , Green RobertC. , Saykin Andrew J. , Morris John , Shaw Leslie M. , Khachaturian Zaven , Sorensen Greg , Carrillo Maria , Kuller Lew , Raichle Marc , Paul Steven , Davies Peter , Fillit Howard , Hefti Franz , Holtzman Davie , Mesulam M. Marcel , Potter William , Snyder Peter , Montine Tom , Thomas Ronald G. , Donohue Michael , Walter Sarah , Sather Tamie , Jiminez Gus , Balasubramanian Archana B. , Mason Jennifer , Sim Iris , Harvey Danielle , Bernstein Matthew , Fox Nick , Thompson Paul , Schuf Norbert , DeCArli Charles , Borowski Bret , Gunter Jef , Senjem Matt , Vemuri Prashanthi , Jones David , Kantarci Kejal , Ward Chad , Koeppe Robert A. , Foster Norm , Reiman Eric M. , Chen Kewei , Mathis Chet , Landau Susan , Cairns Nigel J. , Householder Erin , Taylor-Reinwald Lisa , Lee Virginia , Korecka Magdalena , Figurski Michal , Crawford Karen , Neu Scott , Foroud Tatiana M. , Potkin Steven , Shen Li , Faber Kelley , Kim Sungeun , Tha Lean , Frank Richard , Hsiao John , Kaye Jefrey , Quinn Joseph , Silbert Lisa , Lind Betty , Carter Raina , Dolen Sara , Ances Beau , Carroll Maria , Creech Mary L. , Franklin Erin , Mintun Mark A. , Schneider Stacy , Oliver Angela , Schneider Lon S. , Pawluczyk Sonia , Beccera Mauricio , Teodoro Liberty , Spann Bryan M. , Brewer James , Vanderswag Helen , Fleisher Adam , Marson Daniel , Grifth Randall , Clark David , Geldmacher David , Brockington John , Roberson Erik , Love Marissa Natelson , Heidebrink Judith L. , Lord Joanne L. , Mason Sara S. , Albers Colleen S. , Knopman David , Johnson Kris , Grossman Hillel , Mitsis Efe , Shah Raj C. , deToledo-Morrell Leyla , Doody Rachelle S. , Villanueva-Meyer Javier , Chowdhury Munir , Rountree Susan , Dang Mimi , Duara Ranjan , Varon Daniel , Greig Maria T. , Roberts Peggy , Stern Yaakov , Honig Lawrence S. , Bell Karen L. , Albert Marilyn , Onyike Chiadi , D’Agostino Daniel , Kielb Stephanie , Galvin James E. , Cerbone Brittany , Michel Christina A. , Pogorelec Dana M. , Rusinek Henry , de Leon Mony J. , Glodzik Lidia , De Santi Susan , Womack Kyle , Mathews Dana , Quiceno Mary , Doraiswamy P. Murali , Petrella Jefrey R. , Borges-Neto Salvador , Wong Terence Z. , Coleman Edward , Levey Allan I. , Lah James J. , Cella Janet S. , Burns Jefrey M. , Swerdlow Russell H. , Brooks William M. , Arnold Steven E. , Karlawish Jason H. , Wolk David , Clark Christopher M. , Apostolova Liana , Tingus Kathleen , Woo Ellen , Silverman Daniel H. S. , Lu Po H. , Bartzokis George , Smith Charles D. , Jicha Greg , Hardy Peter , Sinha Partha , Oates Elizabeth , Conrad Gary , Graf-Radford Neill R. , Parftt Francine , Kendall Tracy , Johnson Heather , Lopez Oscar L. , Oakley MaryAnn , Simpson Donna M. , Farlow Martin R. , Hake Ann Marie , Matthews Brandy R. , Brosch Jared R. , Herring Scott , Hunt Cynthia , Porsteinsson Anton P. , Goldstein Bonnie S. , Martin Kim , Makino Kelly M. , Ismail M. Saleem , Brand Connie , Mulnard Ruth A. , Thai Gaby , Mc-Adams-Ortiz Catherine , van Dyck Christopher H. , Carson Richard E. , MacAvoy Martha G. , Varma Pradeep , Chertkow Howard , Bergman Howard , Hosein Chris , Black Sandra , Stefanovic Bojana , Caldwell Curtis , Hsiung Ging-Yuek Robin , Feldman Howard , Mudge Benita , Assaly Michele , Finger Elizabeth , Pasternack Stephen , Rachisky Irina , Trost Dick , Kertesz Andrew , Bernick Charles , Munic Donna , Lipowski Kristine , Weintraub Masandra , Bonakdarpour Borna , Kerwin Diana , Wu Chuang-Kuo , Johnson Nancy , Sadowsky Carl , Villena Teresa , Turner Raymond Scott , Johnson Kathleen , Reynolds Brigid , Sperling Reisa A. , Johnson Keith A. , Marshall Gad , Yesavage Jerome , Taylor Joy L. , Lane Barton , Rosen Allyson , Tinklenberg Jared , Sabbagh Marwan N. , Belden Christine M. , Jacobson Sandra A. , Sirrel Sherye A. , Kowall Neil , Killiany Ronald , Budson Andrew E. , Norbash Alexander , Johnson Patricia Lynn , Obisesan Thomas O. , Wolday Saba , Allard Joanne , Lerner Alan , Ogrocki Paula , Tatsuoka Curtis , Fatica Parianne , Fletcher Evan , Maillard Pauline , Olichney John , Carmichael Owen , Kittur Smita , Borrie Michael , Lee T.-Y. , Bartha Rob , Johnson Sterling , Asthana Sanjay , Carlsson Cynthia M. , Preda Adrian , Nguyen Dana , Tariot Pierre , Burke Anna , Trncic Nadira , Fleisher Adam , Reeder Stephanie , Bates Vernice , Capote Horacio , Rainka Michelle , Scharre Douglas W. , Kataki Maria , Adeli Anahita , Zimmerman Earl A. , Celmins Dzintra , Brown Alice D. , Pearlson Godfrey D. , Blank Karen , Anderson Karen , Flashman Laura A. , Seltzer Marc , Hynes Mary L. , Santulli Robert B. , Sink Kaycee M. , Gordineer Leslie , Williamson Jef D. , Garg Pradeep , Watkins Franklin , Ott Brian R. , Querfurth Henry , Tremont Geofrey , Salloway Stephen , Malloy Paul , Correia Stephen , Rosen Howard J. , Miller Bruce L. , Perry David , Mintzer Jacobo , Spicer Kenneth , Bachman David , Finger Elizabether , Pasternak Stephen , Rachinsky Irina , Rogers John , Drost Dick , Pomara Nunzio , Hernando Raymundo , Sarrael Antero , Schultz Susan K. , Ponto Laura L. Boles , Shim Hyungsub , Smith Karen Ekstam , Relkin Norman , Chaing Gloria , Lin Michael , Ravdin Lisa , Smith Amanda , Raj Balebail Ashok , Fargher Kristin 
Published: July 2021

Alzheimer’s disease (AD) is a complex and heterogeneous disease that can be affected by various genetic factors. Although the cause of AD is not yet known and there is no treatment to cure this disease, its progression can be delayed. AD has recently been recognized as a brain-specific type of diabetes called type 3 diabetes. Several studies have shown that people with type 2 diabetes (T2D) have a higher risk of developing AD. Therefore, it is important to identify subgroups of patients with AD that may be more likely to be associated with T2D. We here describe a new approach to identify the correlation between AD and T2D at the genetic level. Subgroups of AD and T2D were each generated using a non-negative matrix factorization (NMF) approach, which generated clusters containing subsets of genes and samples. In the gene cluster that was generated by conventional gene clustering method from NMF, we selected genes with significant differences in the corresponding sample cluster by Kruskal–Wallis and Dunn-test. Subsequently, we extracted differentially expressed gene (DEG) subgroups, and candidate genes with the same regulation direction can be extracted at the intersection of two disease DEG subgroups. Finally, we identified 241 candidate genes that represent common features related to both AD and T2D, and based on pathway analysis we propose that these genes play a role in the common pathological features of AD and T2D. Moreover, in the prediction of AD using logistic regression analysis with an independent AD dataset, the candidate genes obtained better prediction performance than DEGs. In conclusion, our study revealed a subgroup of patients with AD that are associated with T2D and candidate genes associated between AD and T2D, which can help in providing personalized and suitable treatments.