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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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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

Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade

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

The amyloid hypothesis of Alzheimer's disease at 25 years

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.
References
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Journal ArticleDOI

Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices

TL;DR: The number of Thioflavine S-positive neurofibrillary tangles and neuritic plaques determined in visual and auditory cortical regions of 8 patients with Alzheimer's disease suggests that NFT reside in the cell bodies of a subpopulation of pyramidal neurons, namely, those that furnish long corticocortical projections in homologous regions of monkey neocortex.
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Pathologic correlates of nondemented aging, mild cognitive impairment, and early-stage Alzheimer's disease.

TL;DR: It is concluded that widespread amyloid plaques in the neocortex best distinguishes very early stage AD, including “MCI” stage, and preclinical stages, from healthy brain aging and it is now critical to develop methods to detect preclinical AD during life.
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Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with [18F]fluorodeoxyglucose.

TL;DR: Positron emission tomography is a most powerful tool for the noninvasive in vivo assessment of cerebral pathophysiology in dementia and suggests that the metabolic effects of Alzheimer disease are most concentrated in the temporoparietal cortex.
Journal ArticleDOI

Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer’s Disease Treatment Studies

TL;DR: It is indicated that brain metabolism as assessed by FDG PET during mental rest is a sensitive marker of disease progression in Alzheimer's disease over a 1-year period and the feasibility of usingFDG PET as an outcome measure to test the ability of treatments to attenuate the progression of dementia is supported.
Journal ArticleDOI

Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain.

TL;DR: The combination of relatively high affinity for amyloid, specificity for staining plaques and neurofibrillary tangles in post-mortem AD brain, and good brain entry and clearance makes [N-methyl-11C]6-Me-BTA-1 a promising candidate as an in vivo positron emission tomography (PET) beta-sheet imaging agent.
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