Insulin-like growth factor binding protein-2 in at-risk adults and autopsy-confirmed Alzheimer brains

队列 无症状的 内科学 海马体 痴呆 医学 阿尔茨海默病 肿瘤科 内分泌学 人口 病理 心理学 神经科学 疾病 环境卫生
作者
Marc James Quesnel,Anne Labonté,Cynthia Picard,Henrik Zetterberg,Kaj Blennow,Ann Brinkmalm,Sylvia Villeneuve,Judes Poirier,Michael W. Weiner,Paul S. Aisen,Ronald C. Petersen,Michael W Weiner,Paul S. Aisen,Ronald Petersen,Clifford R. Jack,William J. Jagust,John Q. Trojanowki,Arthur W. Toga,Laurel Beckett,Robert C Green,Andrew J. Saykin,John C. Morris,Richard J. Perrin,Leslie M. Shaw,Zaven S. Khachaturian,Maria Carrillo,William Z. Potter,Lisa L. Barnes,Marie Bernard,Héctor Alfredo Baptista González,Carole Ho,John Hsiao,Jonathan Jackson,Eliezer Masliah,Donna Masterman,Ozioma C. Okonkwo,Richard J. Perrin,Laurie Ryan,Nina Silverberg,Adam Fleisher,Michael W Weiner,Diana Truran Sacrey,Juliet Fockler,Cat Conti,Dallas P. Veitch,John Neuhaus,Chengshi Jin,Rachel L. Nosheny,Miriam T. Ashford,Derek Flenniken,Adrienne Kormos,Robert C. Green,Tom Montine,Cat Conti,Ronald Petersen,Paul S. Aisen,Michael S. Rafii,Rema Raman,Gustavo Jiménez,Michael Donohue,Devon Gessert,Jennifer Salazar,Caileigh Zimmerman,Yuliana Cabrera,Sarah Walter,Garrett Miller,Godfrey Coker,Taylor Clanton,Lindsey Hergesheimer,Stephanie Smith,Olusegun Adegoke,Payam Mahboubi,Shelley Moore,Jeremy Pizzola,Elizabeth Shaffer,Brittany Sloan,Laurel Beckett,Danielle Harvey,Michael Donohue,Clifford R. Jack,Arvin Forghanian-Arani,Bret Borowski,Chad Ward,Christopher G. Schwarz,David Jones,Jeff Gunter,Kejal Kantarci,Matthew L. Senjem,Prashanthi Vemuri,Robert I. Reid,Nick C. Fox,Ian B. Malone,Paul M. Thompson,Sophia I. Thomopoulos,Talia M. Nir,Neda Jahanshad,Charles DeCarli,Alexander Knaack,E. Fletcher,Danielle Harvey,Duygu Tosun,Stephanie Rossi Chen,Mark Choe,Karen Crawford,Paul A. Yushkevich,Sandhitsu R. Das,William J. Jagust,Robert A. Koeppe,Eric M. Reiman,Kewei Chen,Chester A. Mathis,Susan Landau,John C. Morris,Richard J. Perrin,Nigel J. Cairns,Erin Householder,Erin Franklin,H R,L. Taylor-Reinwald,Leslie M. Shaw,John Q. Trojanowki,Magdalena Korecka,Michal Figurski,Arthur W. Toga,Karen Crawford,Scott Neu,Andrew J. Saykin,Kwangsik Nho,Shannon L. Risacher,Liana G. Apostolova,Li Shen,Tatiana Foroud,Kelly Nudelman,Kelley Faber,Kristi Wilmes,Michael W Weiner,Leon J. Thal,Zaven S. Khachaturian,John Hsiao,Lisa C. Silbert,Betty Lind,Rachel Crissey,Jeffrey Kaye,Raina Carter,Sara Dolen,Joseph Quinn,Lon S. Schneider,Sonia Pawluczyk,Mauricio Becerra,Liberty Teodoro,Karen Dagerman,Bryan M. Spann,James B. Brewer,Helen Vanderswag,Adam Fleisher,Jaimie Ziolkowski,Judith L. Heidebrink,M S Lisa Zbizek-Nulph,Joanne Lord,Lisa Zbizek-Nulph,Ronald Petersen,Sara S. Mason,Colleen S. Albers,David S. Knopman,Kris Johnson,Javier Villanueva-Meyer,Valory Pavlik,Nathaniel Pacini,Ashley Lamb,Joseph S. Kass,Rachelle S. Doody,Victoria Shibley,Munir Chowdhury,Mimi Dang,Yaakov Stern,Lawrence S. Honig,Akiva Mintz,Beau M. Ances,John C. Morris,David Winkfield,Maria Carroll,Georgia Stobbs-Cucchi,Angela Oliver,Mary L. Creech,Mark A. Mintun,Stacy Schneider,David Geldmacher,Marissa Natelson Love,Randall Griffith,David Clark,John Brockington,Daniel Marson,Hillel Grossman,Martin Goldstein,Jonathan Greenberg,Effie Mitsis,Raj C. Shah,Melissa Lamar,Ranjan Duara,Maria T. Greig‐Custo,Rosemarie Rodriguez,Marilyn Albert,Chiadi Onyike,Leonie Farrington,Scott Rudow,Rottislav Brichko,Stephanie Kielb,Amanda Smith,Balebail Ashok Raj,Kristin Fargher,Martin Sadowski,Thomas Wısnıewskı,Melanie Shulman,Arline Faustin,Julia Rao,Karen M. Castro,Anaztasia Ulysse,Shannon Chen,Mohammed O. Sheikh,Jamika Singleton-Garvin,P. Murali Doraiswamy,Jeffrey R. Petrella,Olga James,Terence Z. Wong,Salvador Borges‐Neto,Jason Karlawish,David A. Wolk,Sanjeev Vaishnavi,Christopher M. Clark,Steven E. Arnold,Charles D. Smith,Gregory A. Jicha,Riham El Khouli,Flavius D. Raslau,Oscar L. López,MaryAnn Oakley,Donna M. Simpson,Anton P. Porsteinsson,Kim Martin,Nancy Kowalski,Melanie Keltz,Bonnie S. Goldstein,Kelly M. Makino,M. Saleem Ismail,Connie Brand,Gaby Thai,Aimee Pierce,Beatriz Yáñez‐Rivera,Elizabeth Sosa,Megan Witbracht,Brendan Kelley,Trung Dung Nguyen,Kyle Womack,Dana Mathews,Mary Quiceno,Allan I. Levey,James J. Lah,Ihab Hajjar,Janet S. Cellar,Jeffrey M. Burns,Russell H. Swerdlow,William M. Brooks,Daniel Silverman,Sarah Kremen,Liana G. Apostolova,Kathleen Tingus,Haonan Lu,George Bartzokis,Ellen Woo,Edmond Teng,Neill R. Graff‐Radford,Francine Parfitt,Kim Poki-Walker,Martin R. Farlow,Ann Marie Hake,Brandy R. Matthews,Jared R. Brosch,Scott Herring,Christopher H. van Dyck,Adam P. Mecca,Adam P. Mecca,Susan P. Good,Martha G. MacAvoy,Richard E. Carson,Pradeep Varma,Howard Chertkow,Susan Vaitekunis,Chris Hosein,Sandra E. Black,Bojana Stefanovic,Chris Heyn,Ging‐Yuek Robin Hsiung,Ellen Kim,Benita Mudge,Vesna Sossi,Howard Feldman,Michele Assaly,Elizabeth Finger,Stephen Pasternak,Irina Rachinsky,Andrew Kertesz,Dick Drost,John Rogers,Ian Grant,Brittanie Muse,Emily Rogalskı,Jordan Robson,M-Marsel Mesulam,Diana Kerwin,Chuang‐Kuo Wu,Nancy E. Johnson,Kristine Lipowski,Sandra Weıntraub,Borna Bonakdarpour,Nunzio Pomara,Raymundo Hernando,Antero Sarrael,Howard J. Rosen,Bruce L. Miller,David C. Perry,Raymond Scott Turner,Kathleen Johnson,Brigid Reynolds,Kelly McCann,Jessica Poe,Reisa A. Sperling,Keith A. Johnson,Gad A. Marshall,Jerome A. Yesavage,Joy L. Taylor,Steven Chao,Jaila Coleman,Jessica D. White,Barton Lane,Allyson Rosen,Jared Tinklenberg,Christine M. Belden,Alireza Atri,Bryan M. Spann,Kelly Clark,Edward Zamrini,Marwan Sabbagh,Ronald Killiany,Robert A. Stern,Jesse Mez,Neil W. Kowall,Andrew E. Budson,Thomas O. Obisesan,Oyonumo Ntekim,Saba Wolday,Javed Khan,Evaristus Nwulia,Sheeba Nadarajah,Alan J. Lerner,Paula Ogrocki,Curtis Tatsuoka,Parianne Fatica,E. Fletcher,Pauline Maillard,John Olichney,Charles DeCarli,Owen Carmichael,Vernice Bates,Horacio Capote,Michelle Rainka,Michael Borrie,T-Y Lee,Robert Bartha,Sterling C. Johnson,Sanjay Asthana,Cynthia M. Carlsson,Allison Perrin,Anna Burke,Douglas W. Scharre,Maria Kataki,Rawan Tarawneh,Brendan Kelley,David Hart,Earl A. Zimmerman,Dzintra Celmins,Del D. Miller,Laura L. Boles Ponto,Karen Ekstam Smith,Hristina Koleva,Hyungsub Shim,Ki Won Nam,Susan K. Schultz,Jeff D. Williamson,Mary Craft,Jo Cleveland,Mia Yang,Kaycee M. Sink,Brian R. Ott,Jonathan Drake,Geoffrey Tremont,Lori A. Daiello,Jonathan Drake,Marwan Sabbagh,Aaron Ritter,Charles Bernick,Donna Munic,Akiva Mintz,Abigail O’Connelll,Jacobo Mintzer,Arthur Wiliams,Joseph C. Masdeu,Jiong Shi,Angelica Garcia,Marwan Sabbagh,Paul Newhouse,Steven Potkin,Stephen Salloway,Paul Malloy,Stephen Correia,Smita Kittur,Godfrey D. Pearlson,Karen Blank,Karen Anderson,Laura A. Flashman,Marc Seltzer,Mary L. Hynes,Robert B. Santulli,Norman Relkin,Gloria Chiang,Athena Lee,Michael Lin,Lisa Ravdin,Michael W Weiner,Paul S. Aisen,Ron Petersen,Michael W Weiner,Paul S. Aisen,Ronald Petersen,Robert C Green,Danielle Harvey,Clifford R. Jack,William J. Jagust,John C. Morris,Andrew J. Saykin,Leslie M. Shaw,Arthur W. Toga,John Q. Trojanowki,Thomas C. Neylan,Jordan Grafman,Robert C Green,Tom Montine,Michael W Weiner,Ronald Petersen,Paul S. Aisen,Gustavo Jiménez,Michael Donohue,Devon Gessert,Jennifer Salazar,Caileigh Zimmerman,Sarah Walter,Olusegun Adegoke,Payam Mahboubi,Lindsey Hergesheimer,Sarah Danowski,Godfrey Coker,Taylor Clanton,Jeremy Pizzola,Elizabeth Shaffer,Catherine Nguyen-Barrera,Thomas C. Neylan,Jacqueline Hayes,Shannon Finley,Danielle Harvey,Michael Donohue,Clifford R. Jack,Matt A. Bernstein,Bret Borowski,Jeff Gunter,Matthew L. Senjem,Kejal Kantarci,Chad Ward,Duygu Tosun,Rossi Chen,Susan Landau,Robert A. Koeppe,Norm Foster,Eric M. Reiman,Kewei Chen,John C. Morris,Richard J. Perrin,Erin Franklin,Leslie M. Shaw,John Q. Trojanowki,Magdalena Korecka,Michal Figurski,Arthur W. Toga,Karen Crawford,Scott Neu,Andrew J. Saykin,Tatiana Foroud,Steven Potkin,Li Shen,Kelley Faber,Sung Eun Kim,Kwangsik Nho,Kristi Wilmes,Lon S. Schneider,Sonia Pawluczyk,Mauricio Becerra,Liberty Teodoro,Karen Dagerman,Bryan M. Spann,James B. Brewer,Helen Vanderswag,Adam Fleisher,Yaakov Stern,Lawrence S. Honig,Akiva Mintz,Raj C. Shah,Anil K. Sood,Kimberly S. Blanchard,Debra Fleischman,Konstantinos Arfanakis,Ranjan Duara,Daniel Varon,Maria T. Greig,P. Murali Doraiswamy,Jeffrey R. Petrella,Olga James,Salvador Borges‐Neto,Terence Z. Wong,Anton P. Porsteinsson,Bonnie S. Goldstein,Kimberly S. Martin,Gaby Thai,Aimee Pierce,Christopher Reist,Beatriz Yáñez‐Rivera,Elizabeth Sosa,Megan Witbracht,Carl Sadowsky,Walter Martínez,Teresa Villena,Howard J. Rosen,David C. Perry,Raymond Scott Turner,Kathleen Johnson,Brigid Reynolds,Kelly McCann,Jessica Poe,Reisa A. Sperling,Keith A. Johnson,Gad A. Marshall,Christine M. Belden,Alireza Atri,Bryan M. Spann,Kelly Clark,Edward Zamrini,Marwan Sabbagh,Thomas O. Obisesan,Oyonumo Ntekim,Saba Wolday,Evaristus Nwulia,Sheeba Nadarajah,Sterling C. Johnson,Sanjay Asthana,Cynthia M. Carlsson,Elaine R. Peskind,Eric C. Petrie,Gail Li,Jerome A. Yesavage,Joy L. Taylor,Steven Chao,Jaila Coleman,Jessica D. White,Barton Lane,Allyson Rosen,Jared Tinklenberg,Michael Lin,Gloria Chiang,Lisa Ravdin,Norman Relkin,Abigail O’Connelll,Jacobo Mintzer,Arthur Wiliams,R. Scott Mackin,Paul S. Aisen,Rema Raman,Gustavo Jimenez‐Maggiora,Michael Donohue,Devon Gessert,Jennifer Salazar,Caileigh Zimmerman,Sarah Walter,Olusegun Adegoke,Payam Mahboubi,R. Scott Mackin,Michael W Weiner,Paul S. Aisen,Rema Raman,Clifford R. Jack,Susan Landau,Andrew J. Saykin,Arthur W. Toga,Charles DeCarli,Robert A. Koeppe,Robert C. Green,Erin Drake,Michael W Weiner,Paul S. Aisen,Rema Raman,Mike Donohue,R. Scott Mackin,Craig Nelson,David Bickford,Meryl A. Butters,Michelle Zmuda,Clifford R. Jack,Matt A. Bernstein,Bret Borowski,Jeff Gunter,Matthew L. Senjem,Kejal Kantarci,Chad Ward,Denise Reyes,Robert A. Koeppe,Susan Landau,Arthur W. Toga,Karen Crawford,Scott Neu,Andrew J. Saykin,Tatiana Foroud,Kelley M. Faber,Kwangsik Nho,Kelly Nudelman,R. Scott Mackin,Howard J. Rosen,Craig Nelson,David Bickford,Yiu Ho Au,Kelly Scherer,Daniel Catalinotto,Samuel Stark,Elise Ong,Dariella Fernandez,Meryl A. Butters,Michelle Zmuda,Oscar L. López,MaryAnn Oakley,Donna M. Simpson,Mohammadali Javanray,Sylvia Villeneuve,Judes Poirier,John C.S. Breitner,Sylvain Baillet,Pierre Bellec,Véronique D. Bohbot,M. Mallar Chakravarty,D. Louis Collins,Mahsa Dadar,Simon Ducharme,Alan C. Evans,Maiya R. Geddes,Rick Hoge,Gerhard Multhaup,Lisa‐Marie Munter,Natasha Rajah,Pedro Rosa‐Neto,Jean‐Paul Soucy,R. Nathan Spreng,Christine Tardif,Gabriel Aumont‐Rodrigue,Mohamed Badawy,Julie Bailly,Andrée‐Ann Baril,Lianne Boisvert,Samir Das,Marina Dauar-Tedeschi,Christine Déry,M Elie,Alfonso Fajardo Valdez,Vladimir Fonov,Jonathan Gallago,Claudia Greco,Louise Hudon,Yasser Ituria-Medina,Gabriel Jean,Anne Labonté,Marc Lalancette,Jeannie‐Marie Leoutsakos,Béry Mohammediyan,Pierre Orban,Valentin Ourry,Cynthia Picard,Ting Qiu,Marc James Quesnel,J.-P. Raoult,Jordana Remz,Frédéric St‐Onge,Elisabeth Sylvain,Jennifer Tremblay‐Mercier,Stéphanie Tullo,Étienne Vachon‐Presseau,Yara Yakoub,Pierre Étienne,Serge Gauthier,Vasavan Nair,Jens C. Pruessner,Paul S. Aisen,Elena Anthal,Melissa Appleby,Gülebru Ayrancı,Alan Barkun,Thomas Beaudry,Christophe Bedetti,Fatiha Benbouhoud,Sophie Boutin,Jason Brandt,Leopoldina Carmo,Charles Edouard Carrier,Marianne Chapleau,Laksanun Cheewakriengkrai,Yalin Chen,Blandine Courcot,Doris Couture,Suzanne Craft,A. Claudio Cuello,Christian Dansereau,Leslie-Ann Daoust,Doris Dea,Clément Debacker,René Desautels,Sylvie Dubuc,Guerda Duclair,Marianne Dufour,Mark J. Eisenberg,Rana El-Khoury,Sarah Farzin,Anne-Marie Faubert,Fabiola Ferdinand,David Fontaine,Josée Frappier,Joanne Frenette,Guylaine Gagné,Valérie Gervais,Renuka Giles,Julie Gonneaud,Renee Gordon,Clifford R. Jack,Justin Kat,Christina Kazazian,Zaven S. Khachaturian,David S. Knopman,Theresa Köbe,Penelope Kostopoulos,Marie‐Élyse Lafaille‐Magnan,Gloria Leblond-Baccichet,Tanya Lee,Claude Lepage,Illana Leppert,Cécile Madjar,Laura Mahar,David Maillet,Jean-Robert Maltais,Axel Mathieu,Sulantha Mathotaarachchi,Ginette Mayrand,Melissa McSweeney,Pierre‐François Meyer,Diane Michaud,Justin Miron,Thomas J. Montine,John C. Morris,Jamie Near,Holly Newbold-Fox,Nathalie Nilsson,Hazal Ozlen,Véronique Pagé,Tharick A. Pascoal,Sandra Peillieux,Mirela Petkova,Alexa Pichet Binette,Morteza Pishnamazi,Galina Pogossova,Alexandre Poirier,Marie-Josée Richer,Pierre Rioux,Mark A. Sager,Eunice Farah Saint-Fort,Alyssa Salaciak,Mélissa Savard,Reisa A. Sperling,Cherie Strikwerda‐Brown,Shirin Tabrizi,Angela Tam,Pierre N. Tariot,Eduard Teigner,Louise Théroux,Ronald G. Thomas,Paule‐Joanne Toussaint,Miranda Tuwaig,Isabelle Vallée,Vinod Venugopalan,Sander C.J. Verfaillie,Jacob W. Vogel,Karen Wan,Seqian Wang,Elsa Yu
出处
期刊:Brain [Oxford University Press]
卷期号:147 (5): 1680-1695 被引量:5
标识
DOI:10.1093/brain/awad398
摘要

Abstract Insulin, insulin-like growth factors (IGF) and their receptors are highly expressed in the adult hippocampus. Thus, disturbances in the insulin-IGF signalling pathway may account for the selective vulnerability of the hippocampus to nascent Alzheimer's disease (AD) pathology. In the present study, we examined the predominant IGF-binding protein in the CSF, IGFBP2. CSF was collected from 109 asymptomatic members of the parental history-positive PREVENT-AD cohort. CSF levels of IGFBP2, core AD and synaptic biomarkers were measured using proximity extension assay, ELISA and mass spectrometry. Cortical amyloid-beta (Aβ) and tau deposition were examined using 18F-NAV4694 and flortaucipir. Cognitive assessments were performed during up to 8 years of follow-up, using the Repeatable Battery for the Assessment of Neuropsychological Status. T1-weighted structural MRI scans were acquired, and neuroimaging analyses were performed on pre-specified temporal and parietal brain regions. Next, in an independent cohort, we allocated 241 dementia-free ADNI-1 participants into four stages of AD progression based on the biomarkers CSF Aβ42 and total-tau (t-tau). In this analysis, differences in CSF and plasma IGFBP2 levels were examined across the pathological stages. Finally, IGFBP2 mRNA and protein levels were examined in the frontal cortex of 55 autopsy-confirmed AD and 31 control brains from the Quebec Founder Population (QFP) cohort, a unique population isolated from Eastern Canada. CSF IGFBP2 progressively increased over 5 years in asymptomatic PREVENT-AD participants. Baseline CSF IGFBP2 was positively correlated with CSF AD biomarkers and synaptic biomarkers, and negatively correlated with longitudinal changes in delayed memory (P = 0.024) and visuospatial abilities (P = 0.019). CSF IGFBP2 was negatively correlated at a trend-level with entorhinal cortex volume (P = 0.082) and cortical thickness in the piriform (P = 0.039), inferior temporal (P = 0.008), middle temporal (P = 0.014) and precuneus (P = 0.033) regions. In ADNI-1, CSF (P = 0.009) and plasma (P = 0.001) IGFBP2 were significantly elevated in Stage 2 [CSF Aβ(+)/t-tau(+)]. In survival analyses in ADNI-1, elevated plasma IGFBP2 was associated with a greater rate of AD conversion (hazard ratio = 1.62, P = 0.021). In the QFP cohort, IGFBP2 mRNA was reduced (P = 0.049); however, IGFBP2 protein levels did not differ in the frontal cortex of autopsy-confirmed AD brains (P = 0.462). Nascent AD pathology may induce an upregulation in IGFBP2 in asymptomatic individuals. CSF and plasma IGFBP2 may be valuable markers for identifying CSF Aβ(+)/t-tau(+) individuals and those with a greater risk of AD conversion.
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