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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Journal ArticleDOI
The amyloid beta peptide: a chemist's perspective. Role in Alzheimer's and fibrillization.
TL;DR: The γ-secretase complex and its cell surface localization, in the absence of an effect on Notch, is studied to avoid side-effects caused by EP2 receptor.
Journal ArticleDOI
A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease
Adrian W. Laxton,David F. Tang-Wai,David F. Tang-Wai,Mary Pat McAndrews,Dominik Zumsteg,Richard Wennberg,Ron Keren,John Wherrett,John Wherrett,Gary Naglie,Clement Hamani,Gwenn S. Smith,Andres M. Lozano +12 more
TL;DR: It is hypothesized that fornix/hypothalamus deep brain stimulation (DBS) could modulate neurophysiological activity in these pathological circuits and possibly produce clinical benefits in Alzheimer's disease.
Journal ArticleDOI
Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease
Eric M. Reiman,Kewei Chen,Xiaofen Liu,Daniel Bandy,Meixiang Yu,Wendy Lee,Napatkamon Ayutyanont,Jennifer Keppler,Stephanie A. Reeder,Jessica B. Langbaum,Gene E. Alexander,William E. Klunk,Chester A. Mathis,Julie C. Price,Howard J. Aizenstein,Steven T. DeKosky,Steven T. DeKosky,Richard J. Caselli +17 more
TL;DR: Fibrillar Aβ burden in cognitively normal older people is associated with APOE ε4 gene dose, the major genetic risk factor for AD, and was highest in an additional homozygote who had recently developed mild cognitive impairment.
Journal ArticleDOI
Imaging of Tau Pathology in a Tauopathy Mouse Model and in Alzheimer Patients Compared to Normal Controls
Masahiro Maruyama,Hitoshi Shimada,Tetsuya Suhara,Hitoshi Shinotoh,Bin Ji,Jun Maeda,Ming-Rong Zhang,John Q. Trojanowski,Virginia M.-Y. Lee,Maiko Ono,Kazuto Masamoto,Harumasa Takano,Naruhiko Sahara,Naruhiko Sahara,Nobuhisa Iwata,Nobuyuki Okamura,Shozo Furumoto,Yukitsuka Kudo,Qing Chang,Takaomi C. Saido,Akihiko Takashima,Jada Lewis,Ming Kuei Jang,Ichio Aoki,Hiroshi Ito,Makoto Higuchi +25 more
TL;DR: A class of tau ligands, phenyl/pyridinyl-butadienyl-benzothiazoles/benZothiazoliums (PBBs), for visualizing diverse tau inclusions in brains of living patients with AD or non-AD tauopathies and animal models of these disorders are developed.
Journal ArticleDOI
Brain Imaging in Alzheimer Disease
TL;DR: The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies.
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