心的外傷後ストレス障害およびアルツハイマー病におけるCXCL8の標的化：疾患横断的分子解析からの洞察

Emerging clinical evidence indicates that post-traumatic stress disorder (PTSD) may accelerate Alzheimer's disease progression, yet the molecular mechanisms linking these disorders remain poorly understood.

We conducted an integrative bioinformatics analysis combining blood cell profiles from PTSD and Alzheimer's disease cohorts to identify shared pathogenic pathways and therapeutic targets. Computational drug repositioning and experimental validation were used to pinpoint effective treatments.

Our analysis revealed convergent dysregulation in neuroimmune and metabolic pathways, including compensatory upregulation of terpenoid biosynthesis and impaired JAK-STAT neuroprotective signaling. Cross-disorder network analysis identified CXCL8 as a central hub gene, prioritized through network pharmacology and machine learning. Mechanistic studies demonstrated that CXCL8 is dually regulated by stress-responsive transcriptional activators and neurodegeneration-associated microRNAs, positioning it as a key mediator of peripheral-central immune crosstalk. Immunoassays further linked CXCL8 to T cell recruitment (γδ T, CD8⁺ T), suggesting its role in sustaining neuroinflammation common to both diseases. Among potential therapeutics, nonsteroidal anti-inflammatory drugs emerged as modulators of CXCL8-driven pathology, with ibuprofen significantly suppressing neurodegeneration-associated CXCL8 overexpression.

Our findings highlight CXCL8-mediated neuroimmune dysregulation as a critical link between PTSD and Alzheimer's disease, supporting targeted anti-inflammatory strategies to mitigate stress-related dementia risk. This study advances a precision medicine framework for neurodegenerative comorbidities by integrating cross-disease molecular signatures.