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
TLDR
The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.Abstract:
This report describes the first human study of a novel amyloid-imaging positron emission tomography (PET) tracer, termed Pittsburgh Compound-B (PIB), in 16 patients with diagnosed mild AD and 9 controls. Compared with controls, AD patients typically showed marked retention of PIB in areas of association cortex known to contain large amounts of amyloid deposits in AD. In the AD patient group, PIB retention was increased most prominently in frontal cortex (1.94-fold, p = 0.0001). Large increases also were observed in parietal (1.71-fold, p = 0.0002), temporal (1.52-fold, p = 0.002), and occipital (1.54-fold, p = 0.002) cortex and the striatum (1.76-fold, p = 0.0001). PIB retention was equivalent in AD patients and controls in areas known to be relatively unaffected by amyloid deposition (such as subcortical white matter, pons, and cerebellum). Studies in three young (21 years) and six older healthy controls (69.5 +/- 11 years) showed low PIB retention in cortical areas and no significant group differences between young and older controls. In cortical areas, PIB retention correlated inversely with cerebral glucose metabolism determined with 18F-fluorodeoxyglucose. This relationship was most robust in the parietal cortex (r = -0.72; p = 0.0001). The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.read more
Citations
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The Brain's Default Network Anatomy, Function, and Relevance to Disease
TL;DR: Past observations are synthesized to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment, and for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.
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
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.
Journal ArticleDOI
The amyloid hypothesis of Alzheimer's disease at 25 years
Dennis J. Selkoe,John Hardy +1 more
TL;DR: In a recent study, this article showed that low cerebrospinal fluid (CSF) Aβ42 and amyloid-PET positivity precede other AD manifestations by many years.
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Journal ArticleDOI
Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain.
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