Label-free high-resolution visualization of Alzheimer's disease (AD) neuropathological
hallmark, amyloid beta (A beta) plaques, is one of the prime goals of neuroscience.
Till today, traditional histological procedures, which rely on fixation and tedious
staining of tissues, can only provide definitive confirmation of AD. However, recent
studies have shown that label-free third harmonic generation (THG) microscopy, a virtual
transition based technology, can provide structural information of biological tissues
with subcellular 3D resolution. In this study, using a 1263 nm Cr: Forsterite laser
source, we performed THG studies on 3xTg AD mice brain tissues in vitro, with a focus
on contrast origin evaluation for plaques. Our THG study can clearly differentiate,
with very high resolution, neuropathological hallmark of AD: A beta plaques. Moreover,
THG can also distinguish white and gray matter along with axons, and soma of brain.
The origin of THG contrasts for various structures of brain including AD pathological
hallmarks were verified through standard immunohistochemical staining procedures.
Our preliminary study has successfully demonstrated the capability of THG in revealing
AD histopathological features with sub-femtoliter resolution without the need of any
exogenous staining of the tissues.
