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- W76631440 abstract "Senile plaques found in Alzheimer’s disease (AD) and in transgenic mouse models of AD are comprised primarily of the amyloid-β peptide. We developed an imaging technique using multiphoton microscopy to enable both detection of amyloid-β pathology in living transgenic mice and functional results of amyloid-β deposition. We used this imaging method to characterize the in vivo kinetics of a novel amyloid-binding agent (6-OH-BTA-1, or Pittsburgh compound B, “PIB”) in transgenic mice. PIB is a novel, thioflavin-T analog that stains plaques, tangles and cerebrovascular amyloid in post-mortem sections of AD brain with high sensitivity and specificity that can cross the blood-brain-barrier. Individual plaques in living transgenic mice could be detected within 1 min after i.v. injection of 2–10 mg/kg PIB. Thirty min after iv injection, the fluorescence in the parenchyma was largely diminished, whereas amyloid-β deposits remained brightly labeled. These findings suggest that PIB is a viable candidate as an in vivo amyloid imaging agent that could allow both diagnostic detection of amyloid pathology and provide a biomarker to evaluate anti-amyloid drug efficacy studies in AD. We also exploited a fluorogenic probe of oxidative stress to detect free radical generation in vivo in these mouse models that is associated specifically with dense-core, but not diffuse, amyloid-β deposits. We then extended the use of multiphoton microscopy and 2’,7’-dichlorodihydrofluorescein (DCF) fluorescence to screen anti-oxidants that may serve a protective role against plaque-derived oxidative stress in an ex vivo system. These results suggest that anti-oxidant therapy may play a beneficial role in the treatment of AD." @default.
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- W76631440 date "2004-01-01" @default.
- W76631440 modified "2023-09-27" @default.
- W76631440 title "In Vivo Imaging of Alzheimer Pathology in Transgenic Mice using Multiphoton Microscopy" @default.
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- W76631440 doi "https://doi.org/10.1007/978-3-642-59300-0_4" @default.
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