Comprehensive Multimodal and Multiscale Analysis of Alzheimer Disease in 5xFAD Mice: Optical Spectroscopies, TEM, Neuropathological, and Behavioral Investigations
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2025
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| author | Solanki, Dhruvil Apachigawo, Ishmael Khan, Sazzad Maity, Santanu Alharthi, Fatemah Nasim, Samia Poshtiri, Mohammad Alizadeh Sweety, Fnu Xiao, Jiangfeng Khan, Mohammad Moshahid Pradhan, Prabhakar |
| author_facet | Solanki, Dhruvil Apachigawo, Ishmael Khan, Sazzad Maity, Santanu Alharthi, Fatemah Nasim, Samia Poshtiri, Mohammad Alizadeh Sweety, Fnu Xiao, Jiangfeng Khan, Mohammad Moshahid Pradhan, Prabhakar |
| contents | Alzheimer 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 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 and progression of AD. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2511_18320 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Comprehensive Multimodal and Multiscale Analysis of Alzheimer Disease in 5xFAD Mice: Optical Spectroscopies, TEM, Neuropathological, and Behavioral Investigations Solanki, Dhruvil Apachigawo, Ishmael Khan, Sazzad Maity, Santanu Alharthi, Fatemah Nasim, Samia Poshtiri, Mohammad Alizadeh Sweety, Fnu Xiao, Jiangfeng Khan, Mohammad Moshahid Pradhan, Prabhakar Medical Physics Biological Physics Optics Alzheimer 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 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 and progression of AD. |
| title | Comprehensive Multimodal and Multiscale Analysis of Alzheimer Disease in 5xFAD Mice: Optical Spectroscopies, TEM, Neuropathological, and Behavioral Investigations |
| topic | Medical Physics Biological Physics Optics |
| url | https://arxiv.org/abs/2511.18320 |