The impact of PICALM genetic variations on reserve capacity of posterior cingulate in AD continuum
Authors: Xu Wei , Wang Hui-Fu , Tan Lin , Tan Meng-Shan , Tan Chen-Chen , Zhu Xi-Chen , Miao Dan , Yu Wan-Jiang , Jiang Teng , Tan Lan , Yu Jin-Tai ,   Alzheimer’s Disease Neuroimaging Initiative Group, Weiner Michael W. , Aisen Paul , Petersen Ronald , Jack Clifford R. , Jagust William , Trojanowki John Q. , Toga Arthur W. , Beckett Laurel , Green Robert C. , Saykin Andrew J. , Morris John , Shaw Leslie M. , Kaye Jeffrey , Quinn Joseph , Silbert Lisa , Lind Betty , Carter Raina , Dolen Sara , Schneider Lon S. , Pawluczyk Sonia , Beccera Mauricio , Teodoro Liberty , Spann Bryan M. , Brewer James , Vanderswag Helen , Fleisher Adam , Heidebrink Judith L. , Lord Joanne L. , Mason Sara S. , Albers Colleen S. , Knopman David , Johnson Kris , Doody Rachelle S. , Villanueva-Meyer Javier , Chowdhury Munir , Rountree Susan , Dang Mimi , Stern Yaakov , Honig Lawrence S. , Bell Karen L. , Ances Beau , Morris John C. , Carroll Maria , Creech Mary L. , Franklin Erin , Mintun Mark A. , Schneider Stacy , Oliver Angela , Marson Daniel , Griffith Randall , Clark David , Geldmacher David , Brockington John , Roberson Erik , Natelson Love Marissa , Grossman Hillel , Mitsis Effie , Shah Raj C. , deToledo-Morrell Leyla , Duara Ranjan , Varon Daniel , Greig Maria T. , Roberts Peggy , 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 , Doraiswamy P. Murali , Petrella Jeffrey R. , Borges-Neto Salvador , Wong Terence Z. , Coleman Edward , Smith Charles D. , Jicha Greg , Hardy Peter , Sinha Partha , Oates Elizabeth , Conrad Gary , 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 , Womack Kyle , Mathews Dana , Quiceno Mary , Levey Allan I. , Lah James J. , Cellar Janet S. , Burns Jeffrey M. , Swerdlow Russell H. , Brooks William M. , Apostolova Liana , Tingus Kathleen , Woo Ellen , Silverman Daniel H.S. , Lu Po H. , Bartzokis George , Graff-Radford Neill R. , Parfitt Francine , Kendall Tracy , Johnson Heather , Farlow Martin R. , Hake Ann Marie , Matthews Brandy R. , Brosch Jared R. , Herring Scott , Hunt Cynthia , van Dyck Christopher H. , Carson Richard E. , MacAvoy Martha G. , Varma Pradeep , Chertkow Howard , Bergman Howard , Hosein Chris , Black Sandra , Stefanovic Bojana , Caldwell Curtis , Robin Hsiung Ging-Yuek , Feldman Howard , Mudge Benita , Assaly Michele , Finger Elizabeth , Pasternack Stephen , Rachisky Irina , Trost Dick , Kertesz Andrew , Bernick Charles , Munic Donna , Mesulam Marek-Marsel , Lipowski Kristine , Weintraub Sandra , Bonakdarpour Borna , Kerwin Diana , Wu Chuang-Kuo , Johnson Nancy , Sadowsky Carl , Villena Teresa , Scott Turner Raymond , 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 , Lynn Johnson Patricia , Obisesan Thomas O. , Wolday Saba , Allard Joanne , Lerner Alan , Ogrocki Paula , Tatsuoka Curtis , Fatica Parianne , Fletcher Evan , Maillard Pauline , Olichney John , DeCarli Charles , Carmichael Owen , Kittur Smita , Borrie Michael , Lee T-Y , Bartha Rob , Johnson Sterling , Asthana Sanjay , Carlsson Cynthia M. , Potkin Steven G. , 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 Jeff D. , Garg Pradeep , Watkins Franklin , Ott Brian R. , Querfurth Henry , Tremont Geoffrey , Salloway Stephen , Malloy Paul , Correia Stephen , Rosen Howard J. , Miller Bruce L. , Perry David , Mintzer Jacobo , Spicer Kenneth , Bachman David , Pomara Nunzio , Hernando Raymundo , Sarrael Antero , Relkin Norman , Chaing Gloria , Lin Michael , Ravdin Lisa , Smith Amanda , Ashok Raj Balebail , Fargher Kristin 
Published: April 2016

Phosphatidylinositolbinding clathrin assembly protein (PICALM) gene is one novel genetic player associated with late-onset Alzheimer’s disease (LOAD), based on recent genome wide association studies (GWAS). However, how it affects AD occurrence is still unknown. Brain reserve hypothesis highlights the tolerant capacities of brain as a passive means to fight against neurodegenerations. Here, we took the baseline volume and/or thickness of LOAD-associated brain regions as proxies of brain reserve capacities and investigated whether PICALM genetic variations can influence the baseline reserve capacities and the longitudinal atrophy rate of these specific regions using data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. In mixed population, we found that brain region significantly affected by PICALM genetic variations was majorly restricted to posterior cingulate. In sub-population analysis, we found that one PICALM variation (C allele of rs642949) was associated with larger baseline thickness of posterior cingulate in health. We found seven variations in health and two variations (rs543293 and rs592297) in individuals with mild cognitive impairment were associated with slower atrophy rate of posterior cingulate. Our study provided preliminary evidences supporting that PICALM variations render protections by facilitating reserve capacities of posterior cingulate in non-demented elderly.