Use of Florbetapir-PET for Imaging β-Amyloid Pathology
Christopher M. Clark,Julie A. Schneider,Barry J. Bedell,Thomas G. Beach,Warren B. Bilker,Mark A. Mintun,Michael J. Pontecorvo,Franz Hefti,Alan Carpenter,Matthew Flitter,Michael J. Krautkramer,Hank F. Kung,R. Edward Coleman,P. Murali Doraiswamy,Adam S. Fleisher,Marwan N. Sabbagh,Carl H. Sadowsky,Eric M. Reiman,Simone P. Zehntner,Daniel Skovronsky +19 more
TLDR
Evidence is provided that a molecular imaging procedure can identify β-amyloid pathology in the brains of individuals during life and for the prediction of progression to dementia.Abstract:
Context The ability to identify and quantify brain β-amyloid could increase the accuracy of a clinical diagnosis of Alzheimer disease. Objective To determine if florbetapir F 18 positron emission tomographic (PET) imaging performed during life accurately predicts the presence of β-amyloid in the brain at autopsy. Design, Setting, and Participants Prospective clinical evaluation conducted February 2009 through March 2010 of florbetapir-PET imaging performed on 35 patients from hospice, long-term care, and community health care facilities near the end of their lives (6 patients to establish the protocol and 29 to validate) compared with immunohistochemistry and silver stain measures of brain β-amyloid after their death used as the reference standard. PET images were also obtained in 74 young individuals (18-50 years) presumed free of brain amyloid to better understand the frequency of a false-positive interpretation of a florbetapir-PET image. Main Outcome Measures Correlation of florbetapir-PET image interpretation (based on the median of 3 nuclear medicine physicians' ratings) and semiautomated quantification of cortical retention with postmortem β-amyloid burden, neuritic amyloid plaque density, and neuropathological diagnosis of Alzheimer disease in the first 35 participants autopsied (out of 152 individuals enrolled in the PET pathological correlation study). Results Florbetapir-PET imaging was performed a mean of 99 days (range, 1-377 days) before death for the 29 individuals in the primary analysis cohort. Fifteen of the 29 individuals (51.7%) met pathological criteria for Alzheimer disease. Both visual interpretation of the florbetapir-PET images and mean quantitative estimates of cortical uptake were correlated with presence and quantity of β-amyloid pathology at autopsy as measured by immunohistochemistry (Bonferroni ρ, 0.78 [95% confidence interval, 0.58-0.89]; P Conclusions Florbetapir-PET imaging was correlated with the presence and density of β-amyloid. These data provide evidence that a molecular imaging procedure can identify β-amyloid pathology in the brains of individuals during life. Additional studies are required to understand the appropriate use of florbetapir-PET imaging in the clinical diagnosis of Alzheimer disease and for the prediction of progression to dementia.read more
Citations
More filters
Journal ArticleDOI
NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease
Clifford R. Jack,David A. Bennett,Kaj Blennow,Maria C. Carrillo,Billy Dunn,Samantha Budd Haeberlein,David M. Holtzman,William J. Jagust,Frank Jessen,Jason Karlawish,Enchi Liu,José Luis Molinuevo,Thomas J. Montine,Creighton H. Phelps,Katherine P. Rankin,Christopher C. Rowe,Philip Scheltens,Eric Siemers,Heather M. Snyder,Reisa A. Sperling,Cerise L Elliott,Eliezer Masliah,Laurie M. Ryan,Nina Silverberg +23 more
TL;DR: This research framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms and envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD.
Journal ArticleDOI
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Bruno Dubois,Bruno Dubois,Howard Feldman,Claudia Jacova,Harald Hampel,Harald Hampel,José Luis Molinuevo,Kaj Blennow,Steven T. DeKosky,Serge Gauthier,Dennis J. Selkoe,Randall J. Bateman,Stefano F. Cappa,Sebastian J. Crutch,Sebastiaan Engelborghs,Giovanni B. Frisoni,Nick C. Fox,Douglas Galasko,Marie-Odile Habert,Gregory A. Jicha,Agneta Nordberg,Florence Pasquier,Gil D. Rabinovici,Philippe Robert,Christopher C. Rowe,Stephen Salloway,Marie Sarazin,Stéphane Epelbaum,Stéphane Epelbaum,Leonardo Cruz de Souza,Leonardo Cruz de Souza,Leonardo Cruz de Souza,Bruno Vellas,Pieter Jelle Visser,Lon S. Schneider,Yaakov Stern,Philip Scheltens,Jeffrey L. Cummings +37 more
TL;DR: It is proposed that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease.
Journal ArticleDOI
Applications of Fluorine in Medicinal Chemistry
TL;DR: The effects of the strategic incorporation of fluorine in drug molecules and applications in positron emission tomography are provided, as well as new synthetic methodologies that allow more facile access to a wide range of fluorinated compounds.
Journal ArticleDOI
Clinical Diagnosis of Alzheimer's Disease
TL;DR: There are a number of ways in which a clinical diagnosis of dementia of the Alzheimer type can be made – the application of clinical criteria is the commonest but ancillary techniques such as neuroima are also used.
Journal ArticleDOI
Alzheimer’s Disease: The Challenge of the Second Century
TL;DR: Current information suggests that if the disease is detected before the onset of overt symptoms, it is possible that treatments based on knowledge of underlying pathogenesis can and will be effective.
References
More filters
Journal ArticleDOI
Clinical diagnosis of Alzheimer's disease : report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
Guy M. McKhann,David A. Drachman,Marshall F. Folstein,Robert Katzman,Donald L. Price,Emanuel M. Stadlan +5 more
TL;DR: The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information becomes available.
Journal ArticleDOI
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer's disease
Suzanne S. Mirra,Albert Heyman,Daniel W. McKeel,S. M. Sumi,Barbara J. Crain,L. M. Brownlee,Vogel Fs,James P. Hughes,van Belle G,Leonard Berg +9 more
TL;DR: The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a practical and standardized neuropathology protocol for the postmortem assessment of dementia and control subjects, which provides neuropathologic definitions of such terms as “definite Alzheimer's disease” (AD), “probable AD,” “possible AD” and “normal brain” to indicate levels of diagnostic certainty.
Journal ArticleDOI
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B.
William E. Klunk,Henry Engler,Agneta Nordberg,Yanming Wang,G. Blomqvist,Daniel P. Holt,Mats Bergström,Irina Savitcheva,Guo Feng Huang,Sergio Estrada,Birgitta Ausén,Manik L. Debnath,Julien Barletta,Julie C. Price,Johan Sandell,Brian J. Lopresti,Anders Wall,Pernilla Koivisto,Gunnar Antoni,Chester A. Mathis,Bengt Långström +20 more
TL;DR: The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.
Journal ArticleDOI
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Clifford R. Jack,David S. Knopman,William J. Jagust,Leslie M. Shaw,Paul S. Aisen,Michael W. Weiner,Ronald C. Petersen,John Q. Trojanowski +7 more
TL;DR: This work proposes a model that relates disease stage to AD biomarkers in which Abeta biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and neurodegnerative biomarker become abnormal later, and correlate with clinical symptom severity.
Journal ArticleDOI
Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria
Bruno Dubois,Howard Feldman,Claudia Jacova,Steven T. DeKosky,Pascale Barberger-Gateau,Jeffrey L. Cummings,André Delacourte,Douglas Galasko,Serge Gauthier,Gregory A. Jicha,Kenichi Meguro,John T. O'Brien,Florence Pasquier,Philippe Robert,Martin N. Rossor,Steven Salloway,Yaakov Stern,Pieter Jelle Visser,Philip Scheltens +18 more
TL;DR: The NINCDS-ADRDA and DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientific knowledge as discussed by the authors.
Related Papers (5)
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B.
William E. Klunk,Henry Engler,Agneta Nordberg,Yanming Wang,G. Blomqvist,Daniel P. Holt,Mats Bergström,Irina Savitcheva,Guo Feng Huang,Sergio Estrada,Birgitta Ausén,Manik L. Debnath,Julien Barletta,Julie C. Price,Johan Sandell,Brian J. Lopresti,Anders Wall,Pernilla Koivisto,Gunnar Antoni,Chester A. Mathis,Bengt Långström +20 more
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease
Guy M. McKhann,Guy M. McKhann,David S. Knopman,Howard Chertkow,Bradley T. Hyman,Clifford R. Jack,Claudia H. Kawas,William E. Klunk,Walter J. Koroshetz,Jennifer J. Manly,Richard Mayeux,Richard C. Mohs,John C. Morris,Martin N. Rossor,Philip Scheltens,Maria C. Carrillo,Bill Thies,Sandra Weintraub,Creighton H. Phelps +18 more
Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Reisa A. Sperling,Paul S. Aisen,Laurel A. Beckett,David A. Bennett,Suzanne Craft,Anne M. Fagan,Takeshi Iwatsubo,Clifford R. Jack,Jeffrey Kaye,Thomas J. Montine,Denise C. Park,Eric M. Reiman,Christopher C. Rowe,Eric Siemers,Yaakov Stern,Kristine Yaffe,Maria C. Carrillo,Bill Thies,Marcelle Morrison-Bogorad,Molly V. Wagster,Creighton H. Phelps +20 more