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
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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
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Journal ArticleDOI
Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B.
Ville Leinonen,Irina Alafuzoff,Sargo Aalto,Timo Suotunen,Sakari Savolainen,Kjell Någren,Tero Tapiola,Tuula Pirttilä,Jaakko Rinne,Juha E. Jääskeläinen,Hilkka Soininen,Juha O. Rinne +11 more
TL;DR: This study supports the use of noninvasive [11C]PiB PET in the assessment of Abeta deposition in the brain in patients with and without Alzheimer disease lesions in frontal cortical biopsy specimens.
Journal ArticleDOI
Binding mode of Thioflavin T in insulin amyloid fibrils
Minna Groenning,Mathias Norrman,James M. Flink,Marco van de Weert,Jens T. Bukrinsky,Gerd Schluckebier,Sven Frokjaer +6 more
TL;DR: It is proposed that ThT binds in cavities running parallel to the fibril axis, e.g., between the protofilaments forming the fbrils, which have been proposed previously in insulin fibrils and several other amyloid fibrIL models.
Journal ArticleDOI
Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models
Scott B. Raymond,Lisa H. Treat,Lisa H. Treat,Jonathan D. Dewey,Nathan McDannold,Kullervo Hynynen,Brian J. Bacskai +6 more
TL;DR: It is demonstrated that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques in Alzheimer's mouse models.
Journal ArticleDOI
Effects of Age and Amyloid Deposition on Aβ Dynamics in the Human Central Nervous System
Yafei Huang,Rachel Potter,Wendy Sigurdson,Anna Santacruz,Shirley Shih,Yo-El Ju,Tom Kasten,John C. Morris,Mark A. Mintun,Stephen P. Duntley,Randall J. Bateman +10 more
TL;DR: A reduction in the linear increase in the Aβ levels in CSF samples that is associated with amyloid deposition and a decreased CSF Aβ diurnal pattern associated with increasing age disrupt the normal physiology of Aβ dynamics and may contribute to AD.
Journal ArticleDOI
Alzheimer's disease phenotypes and genotypes associated with mutations in presenilin 2.
Suman Jayadev,James B. Leverenz,James B. Leverenz,Ellen J. Steinbart,Justin Stahl,William E. Klunk,Cheng En Yu,Thomas D. Bird +7 more
TL;DR: It is concluded that mutations in presenilin 2 are rare with only seven being well documented in the literature, and the best studied N141I mutation produces an Alzheimer's disease phenotype with a wide range of onset ages overlapping both early and late onset Alzheimer's Disease.
References
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