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The Journal of Neuroscience, March 15, 2003, 23(6):2212
In Vivo Imaging of Reactive Oxygen Species
Specifically Associated with Thioflavine S-Positive Amyloid Plaques by
Multiphoton Microscopy
Megan E.
McLellan,
Stephen T.
Kajdasz,
Bradley T.
Hyman, and
Brian J.
Bacskai
Massachusetts General Hospital, Department of
Neurology/Alzheimer's Disease Research Laboratory, Charlestown,
Massachusetts 02129
Amyloid- , the primary constituent of senile plaques in
Alzheimer's disease, is hypothesized to cause neuronal damage and cognitive failure, but the mechanisms are unknown. Using multiphoton imaging, we show a direct association between amyloid- deposits and
free radical production in vivo in live, transgenic
mouse models of Alzheimer's disease and in analogous ex
vivo experiments in human Alzheimer tissue. We applied two
fluorogenic compounds, which become fluorescent only after oxidation,
before imaging with a near infrared laser. We observed fluorescence
associated with dense core plaques, but not diffuse plaques, as
determined by subsequent addition of thioflavine S and
immunohistochemistry for amyloid-. Systemic administration of
N-tert-butyl- -phenylnitrone, a free radical spin
trap, greatly reduced oxidation of the probes. These data show directly
that a subset of amyloid plaques produces free radicals in living,
Alzheimer's models and in human Alzheimer tissue. Antioxidant therapy
neutralizes these highly reactive molecules and may therefore be of
therapeutic value in Alzheimer's disease.
Key words:
amyloid-; free radicals; multiphoton; in
vivo imaging; oxidative stress; Alzheimer's disease
Copyright © 2003 Society for Neuroscience 0270-6474/03/2362212-06$05.00/0
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