This research presents our discovery of two new nonlinear optical biomarkers of Alzheimer’s disease (AD), namely 3-photon autofluorescence (3PAF), and Third Harmonic Generation (THG). A hallmark of AD is the aggregation of the Amyloid-Beta (Aβ) protein and Tau protein. Identification of these plaques and analysis of the surrounding cells and tissue is most often done using immunohistochemistry, often with inconsistent results. Using label-free nonlinear optical microscopy, new optical biomarkers were found for identifying a plaque. We present longitudinal imaging of AD progression in mice ranging from 8 to 52 weeks in age, in the hippocampal and cortical regions.
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