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Neurobiol Dis. 2011 Sep;43(3):565-75. doi: 10.1016/j.nbd.2011.05.003. Epub 2011 May 13.

[F-18]FDDNP microPET imaging correlates with brain Aβ burden in a transgenic rat model of Alzheimer disease: effects of aging, in vivo blockade, and anti-Aβ antibody treatment.

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1
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. eteng@ucla.edu

Abstract

In vivo detection of Alzheimer's disease (AD) neuropathology in living patients using positron emission tomography (PET) in conjunction with high affinity molecular imaging probes for β-amyloid (Aβ) and tau has the potential to assist with early diagnosis, evaluation of disease progression, and assessment of therapeutic interventions. Animal models of AD are valuable for exploring the in vivo binding of these probes, particularly their selectivity for specific neuropathologies, but prior PET experiments in transgenic mice have yielded conflicting results. In this work, we utilized microPET imaging in a transgenic rat model of brain Aβ deposition to assess [F-18]FDDNP binding profiles in relation to age-associated accumulation of neuropathology. Cross-sectional and longitudinal imaging demonstrated that [F-18]FDDNP binding in the hippocampus and frontal cortex progressively increases from 9 to 18months of age and parallels age-associated Aβ accumulation. Specificity of in vivo [F-18]FDDNP binding was assessed by naproxen pretreatment, which reversibly blocked [F-18]FDDNP binding to Aβ aggregrates. Both [F-18]FDDNP microPET imaging and neuropathological analyses revealed decreased Aβ burden after intracranial anti-Aβ antibody administration. The combination of this non-invasive imaging method and robust animal model of brain Aβ accumulation allows for future longitudinal in vivo assessments of potential therapeutics for AD that target Aβ production, aggregation, and/or clearance. These results corroborate previous analyses of [F-18]FDDNP PET imaging in clinical populations.

PMID:
21605674
PMCID:
PMC3144750
DOI:
10.1016/j.nbd.2011.05.003
[Indexed for MEDLINE]
Free PMC Article
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