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| Natura: | Preprint |
| Pubblicazione: |
2025
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| Accesso online: | https://arxiv.org/abs/2512.04937 |
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| _version_ | 1866911302157336576 |
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| author | Xutong, She |
| author_facet | Xutong, She |
| contents | Alzheimer's disease (AD) persists as a paramount challenge in neurological research, characterized by the pathological hallmarks of amyloid-$β$ (A$β$) plaques and neurofibrillary tangles composed of hyperphosphorylated tau. This review synthesizes the evolving understanding of AD pathogenesis, moving beyond the linear amyloid cascade hypothesis to conceptualize the disease as a cross-talk of intricately interacting pathologies, encompassing A$β$, tau, and neuroinflammation as the foundation of phase-adapted pathological network model. This evolving pathophysiological understanding parallels a transformation in diagnostic paradigms, where biomarker-based strategies such as the AT(N) framework enable early disease detection during preclinical or prodromal stages. Within this new landscape, while anti-A$β$ monoclonal antibodies (e.g., lecanemab, donanemab), represent a breakthrough as the first disease-modifying therapies, their modest efficacy underscores the limitation of single-target approaches. Therefore, I explore the compelling rationale for combination therapies that simultaneously target A$β$ pathology, aberrant tau, and neuroinflammation. Looking forward, I emphasize emerging technological platforms such as gene editing and biophysical neuromodulation in advancing precision medicine. Ultimately, the integration of early biomarker detection, multi-target therapeutic strategies, and AI-driven patient stratification charts a promising roadmap toward fundamentally altering the trajectory of AD. The future of AD management will be defined by preemptive, biomarker-guided, and personalized combination interventions.
Keywords: Alzheimer's disease, amyloid-$β$, tau pathology, neuroinflammation, combination therapy, multi-target therapy, precision medicine, biomarkers |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2512_04937 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | A Systemic Pathological Network Model and Combinatorial Intervention Strategies for Alzheimer's Disease Xutong, She Molecular Networks Alzheimer's disease (AD) persists as a paramount challenge in neurological research, characterized by the pathological hallmarks of amyloid-$β$ (A$β$) plaques and neurofibrillary tangles composed of hyperphosphorylated tau. This review synthesizes the evolving understanding of AD pathogenesis, moving beyond the linear amyloid cascade hypothesis to conceptualize the disease as a cross-talk of intricately interacting pathologies, encompassing A$β$, tau, and neuroinflammation as the foundation of phase-adapted pathological network model. This evolving pathophysiological understanding parallels a transformation in diagnostic paradigms, where biomarker-based strategies such as the AT(N) framework enable early disease detection during preclinical or prodromal stages. Within this new landscape, while anti-A$β$ monoclonal antibodies (e.g., lecanemab, donanemab), represent a breakthrough as the first disease-modifying therapies, their modest efficacy underscores the limitation of single-target approaches. Therefore, I explore the compelling rationale for combination therapies that simultaneously target A$β$ pathology, aberrant tau, and neuroinflammation. Looking forward, I emphasize emerging technological platforms such as gene editing and biophysical neuromodulation in advancing precision medicine. Ultimately, the integration of early biomarker detection, multi-target therapeutic strategies, and AI-driven patient stratification charts a promising roadmap toward fundamentally altering the trajectory of AD. The future of AD management will be defined by preemptive, biomarker-guided, and personalized combination interventions. Keywords: Alzheimer's disease, amyloid-$β$, tau pathology, neuroinflammation, combination therapy, multi-target therapy, precision medicine, biomarkers |
| title | A Systemic Pathological Network Model and Combinatorial Intervention Strategies for Alzheimer's Disease |
| topic | Molecular Networks |
| url | https://arxiv.org/abs/2512.04937 |