In Vivo Imaging of Reactive Oxygen Species Specifically Associated with Thioflavine S-positive Amyloid Plaques by Multiphoton Microscopy

Overview

Journal J Neurosci

Specialty Neurology

Date 2003 Mar 27

PMID 12657680

Citations 64

Authors

Megan E McLellan

Stephen T Kajdasz

Bradley T Hyman

Brian J Bacskai

Affiliations

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Abstract

Amyloid-beta, 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-beta 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-beta. Systemic administration of N-tert-butyl-alpha-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.

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