Dual Photonics Probing of Nano- to Submicron-Scale Structural Alterations in Human Brain Tissues/Cells and Chromatin/DNA with the Progression of Alzheimer's Disease.

Understanding alterations in structural disorders in tissue/cells/building blocks, such as DNA/chromatin in the human brain, at the nano to submicron level provides us with efficient biomarkers for Alzheimer's detection. Here, we report a dual photonics technique to detect nano- to submicron-scale alterations in brain tissues/cells and DNA/chromatin due to the early to late progression of Alzheimer's disease in humans. Using a recently developed mesoscopic light transport technique, fine-focused nano-sensitive partial wave spectroscopy (PWS), we measure the degree of structural disorder in tissues. Furthermore, the chemical-specific inverse participation ratio technique (IPR) was used to measure the DNA/chromatin structural alterations. The results of the PWS and IPR experiments showed a significant increase in the degree of structural disorder at the nano to submicron scale at different stages of AD relative to their controls for both the tissue/cell and DNA cellular levels. The increase in the structural disorder in cells/tissues and DNA/chromatin in the nuclei can be attributed to higher mass density fluctuations in the tissue and DNA/chromatin damage in the nuclei caused by the rearrangements of macromolecules due to the deposition of the amyloid beta protein and damage in DNA/chromatin with the progress of AD.