Multiomics Reveals Biological Mechanisms Linking Macroscale Structural Covariance Network Dysfunction With Neuropsychiatric Symptoms Across the Alzheimer’s Disease Continuum

作者：Jiwei Jiang, Kun Zhao, Wenyi Li, Peiyang Zheng, Shirui Jiang, Qiwei Ren, Yunyun Duan, Huiying Yu, Xiaopeng Kang, Junjie Li, Ke Hu, Tianlin Jiang, Min Zhao, Linlin Wang, Shi‐Yi Yang, Huiying Zhang, Yaou Liu, Yaou Liu, Anxin Wang, Yong Liu, Yong Liu, Jun Xu · 发表于：Biological Psychiatry · 年份：2024 · DOI：10.1016/j.biopsych.2024.08.027 · 被引用次数：9 · 研究领域：Radiomics and Machine Learning in Medical Imaging、Genetic Associations and Epidemiology、Functional Brain Connectivity Studies

BACKGROUND: The high heterogeneity of neuropsychiatric symptoms (NPSs) hinders further exploration of their role in neurobiological mechanisms and Alzheimer's disease (AD). We aimed to delineate NPS patterns based on brain macroscale connectomics to understand the biological mechanisms of NPSs on the AD continuum. METHODS: We constructed regional radiomics similarity networks for 550 participants (AD with NPSs [n = 376], AD without NPSs [n = 111], and normal control participants [n = 63]) from the CIBL (Chinese Imaging, Biomarkers, and Lifestyle) study. We identified regional radiomics similarity network connections associated with NPSs and then clustered distinct subtypes of AD with NPSs. An independent dataset (n = 189) and internal validation were performed to assess the robustness of the NPS subtypes. Subsequent multiomics analysis was performed to assess the distinct clinical phenotype and biological mechanisms in each NPS subtype. RESULTS: AD patients with NPSs were clustered into severe (n = 187), moderate (n = 87), and mild (n = 102) NPS subtypes, each exhibiting distinct brain network dysfunction patterns. A high level of consistency in clustering NPSs was internally and externally validated. Severe and moderate NPS subtypes were associated with significant cognitive impairment, increased plasma p-tau181 (tau phosphorylated at threonine 181) levels, extensive decreased brain volume and cortical thickness, and accelerated cognitive decline. Gene set enrichment analysi...