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Journal ArticleDOI

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

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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.

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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.

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

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

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

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.

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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Journal ArticleDOI

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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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