# Comprehensive Multimodal and Multiscale Analysis of Alzheimer’s Disease in 5xFAD Mice: Optical Spectroscopies, TEM, Neuropathological, and Behavioral Investigations

## TL;DR

This study uses multiple techniques to analyze Alzheimer’s disease in 5xFAD mice, revealing early structural and behavioral changes that could help detect the disease earlier.

## Contribution

The study introduces PWS and IPR as sensitive biophysical tools for detecting early AD-related structural changes in brain tissues.

## Key findings

- 5xFAD mice showed increased structural heterogeneity and mass density fluctuations in brain tissues.
- Behavioral tests revealed memory impairment in 5xFAD mice compared to controls.
- Histopathology showed more amyloid beta plaques and microglia activation in 5xFAD mice.

## Abstract

Alzheimer’s disease (AD) is considered one of the leading causes of death in the United States, and there is no effective cure for it. Understanding the neuropathological mechanisms underlying AD is essential for identifying early, reliable biomarkers and developing effective therapies. In this paper, we report on a comprehensive multimodal study of AD pathology using the 5xFAD mouse model. We employed light-scattering techniques, Partial Wave Spectroscopy (PWS) and Inverse Participation Ratio (IPR), to detect nanoscale structural alterations in brain tissues, nuclear components, and mitochondria. To support the light-scattering experiments, behavior, and histopathological studies were conducted. These analyses revealed significant increases in structural heterogeneity and mass density fluctuations in the brains of 5xFAD mice compared with Non-transgenic controls. Behavioral assessment performed using the Novel Object Recognition test demonstrated memory impairment in 5xFAD mice, reflected by a reduced recognition index. Histopathological analysis further revealed increased amyloid beta plaques and microglia activation in the hippocampus and cortex of 5xFAD mice compared with Non-transgenic controls. An increase in structural disorder within brain tissues can be attributed to higher mass density fluctuations, likely arising from macromolecular rearrangement driven by amyloid beta aggregation and neuroinflammatory responses as the disease progresses. Our findings suggest that PWS and IPR-derived metrics provide sensitive biophysical indicators of early cellular and subcellular disruption, offering potential as quantitative biomarkers for the detection of AD.