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Journal ArticleDOI

Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B.

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.

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Citations
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Journal ArticleDOI

Small Molecule Microarrays Enable the Discovery of Compounds That Bind the Alzheimer’s Aβ Peptide and Reduce its Cytotoxicity

TL;DR: It is demonstrated that the SMM screen for binding to Aβ is effective at identifying compounds that reduce Aβ toxicity, and can reveal potential therapeutic leads without the biases inherent in methods that focus on inhibitors of aggregation.
Journal ArticleDOI

Phosphodiesterase-4 (PDE4) molecular pharmacology and Alzheimer's disease.

TL;DR: The family of PDE4 enzymes provides rich opportunities for the development of mechanistically novel drugs to treat neuroinflammation or the cognitive deficits in AD, especially for those patients with non-amyloid AD.
Journal ArticleDOI

Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study

TL;DR: While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger, and as neurodegeneration progresses, hippocampal atrophy and not Aβ seems to drive memory decline.
Journal ArticleDOI

[18F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasia.

TL;DR: Semantic dementia provides a useful model in which to test the specificity of in vivo binding of the putative tau ligand [18F]AV-1451, which is elevated in frontotemporal lobar degeneration tauopathies.
References
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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

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

Neuropathological stageing of Alzheimer-related changes.

Heiko Braak, +1 more
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Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data:

TL;DR: A theoretical model of blood–brain exchange is developed and a procedure is derived that can be used for graphing multiple-time tissue uptake data and determining whether a unidirectional transfer process was dominant during part or all of the experimental period.
Journal ArticleDOI

Phases of Aβ-deposition in the human brain and its relevance for the development of AD

TL;DR: Aβ-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved and expands anterogradely into regions that receive neuronal projections from regions already exhibiting Aβ.
Journal ArticleDOI

Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data. Generalizations:

TL;DR: General equations are derived that can be used to analyze tissue uptake data when the blood–plasma concentration of the test substance cannot be easily measured and for situations when trapping of theTest substance is incomplete and for a combination of these two conditions.
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