Dataset Information

Positron emission tomography imaging of fibrillar parenchymal and vascular amyloid-? in TgCRND8 mice.

ABSTRACT: Few quantitative diagnostic and monitoring, tools are available to clinicians treating patients with Alzheimer's disease. Further, many of the promising quantitative imaging tools under development lack clear specificity toward different types of Amyloid-? (A?) pathology such as vascular or oligomeric species. Antibodies offer an opportunity to image specific types of A? pathology because of their excellent specificity. In this study, we developed a method to translate a panel of anti-A? antibodies, which show excellent histological performance, into live animal imaging contrast agents. In the TgCRND8 mouse model of Alzheimer's disease, we tested two antibodies, M64 and M116, that target parenchyma aggregated A? plaques and one antibody, M31, that targets vascular A?. All three antibodies were administered intravenously after labeling with both poly(ethylene glycol) to enhance circulation and (64)Cu to allow detection via positron emission tomography (PET) imaging. We were clearly able to differentiate TgCRND8 mice from wild type controls by PET imaging using either M116, the anti-A? antibody targeting parenchymal A? or M31, the antivascular A? antibody. To confirm the validity of the noninvasive imaging of specific A? pathology, brains were examined after imaging and showed clear evidence of binding to A? plaques.

SUBMITTER: McLean D

PROVIDER: S-EPMC3629748 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Positron emission tomography imaging of fibrillar parenchymal and vascular amyloid-β in TgCRND8 mice.

McLean Daniel D Cooke Michael J MJ Albay Ricardo R Glabe Charles C Shoichet Molly S MS

ACS chemical neuroscience 20130319 4

Few quantitative diagnostic and monitoring, tools are available to clinicians treating patients with Alzheimer's disease. Further, many of the promising quantitative imaging tools under development lack clear specificity toward different types of Amyloid-β (Aβ) pathology such as vascular or oligomeric species. Antibodies offer an opportunity to image specific types of Aβ pathology because of their excellent specificity. In this study, we developed a method to translate a panel of anti-Aβ antibod ...[more]

PMID: 23509918

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Project description:BackgroundDown syndrome appears to be associated with a virtually certain risk of fibrillar amyloid-β (Aβ) pathology by the age of 40 and a very high risk of dementia at older ages. The positron emission tomography (PET) ligand florbetapir F18 has been shown to characterize fibrillar Aβ in the living human brain and to provide a close correlation with subsequent Aβ neuropathology in individuals proximate to and after the end of life. The extent to which the most frequently used PET ligands can be used to detect fibrillar Aβ in patients with Down syndrome remains to be determined.ObjectivesTo characterize PET estimates of fibrillar Aβ burden in a Down syndrome patient very close to the end of life and to compare them with neuropathologic assessment made after his death. Design/MethodsWith the family's informed consent, florbetapir PET was used to study a 55-year-old Down syndrome patient with Alzheimer disease near the end of life; his brain was donated for neuropathologic assessment when he died 14 days later. Visual ratings of cerebral florbetapir uptake were performed by trained readers who were masked to the patient's diagnosis as part of a larger study, and an automated algorithm was used to characterize regional-to-cerebellar standard uptake value ratios in 6 cerebral regions of interest. Neuropathologic assessments were performed masked to the patient's diagnosis or PET measurements.ResultsVisual ratings and automated analyses of the PET image revealed a heavy fibrillar Aβ burden in cortical, striatal, and thalamic regions, similar to that reported for patients with late-onset Alzheimer disease. This matched neuropathologic findings of frequent neuritic and diffuse plaques, as well as frequent amyloid angiopathy, except for neuropathologically demonstrated frequent cerebellar diffuse plaques and amyloid angiopathy that were not detected by the PET scan.ConclusionsFlorbetapir PET can be used to detect increased cerebral-to-cerebellar fibrillar Aβ burden in a Down syndrome patient with Alzheimer disease, even in the presence of frequent amyloid angiopathy and diffuse plaques in the cerebellum. Additional studies are needed to determine the extent to which PET could be used to detect and to track fibrillar Aβ and to evaluate investigational Aβ-modifying treatments in the presymptomatic and symptomatic stages of Alzheimer disease.

Dataset Information

Positron emission tomography imaging of fibrillar parenchymal and vascular amyloid-? in TgCRND8 mice.

Publications

Positron emission tomography imaging of fibrillar parenchymal and vascular amyloid-β in TgCRND8 mice.

Similar Datasets

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