Amanullah Amir A, Mirbod Melika, Pandey Aarti, Singh Shashi B, Gandhi Om H, Ayubcha Cyrus
Jefferson Einstein Montgomery Hospital, Norristown, PA 19403, USA.
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Imaging. 2025 Aug 19;11(8):280. doi: 10.3390/jimaging11080280.
Positron emission tomography (PET) has become a powerful tool in Alzheimer's disease (AD) research by enabling in vivo visualization of pathological biomarkers. Recent efforts have aimed to integrate PET-derived imaging phenotypes with genome-wide association studies (GWASs) to better elucidate the genetic architecture underlying AD. This systematic review examines studies that leverage PET imaging in the context of GWASs (PET-GWASs) to identify genetic variants associated with disease risk, progression, and brain region-specific pathology. A comprehensive search of PubMed and Embase databases was performed on 18 February 2025, yielding 210 articles, of which 10 met pre-defined inclusion criteria and were included in the final synthesis. Studies were eligible if they included AD populations, employed PET imaging alongside GWASs, and reported original full-text findings in English. No formal protocol was registered, and the risk of bias was not independently assessed. The included studies consistently identified as the strongest genetic determinant of amyloid burden, while revealing additional significant loci including ABCA7 (involved in lipid metabolism and amyloid clearance), (cell adhesion), (immune response), TOMM40 (mitochondrial function), and (protective against amyloid deposition in Korean populations). The included studies suggest that PET-GWAS approaches can uncover genetic loci involved in processes such as lipid metabolism, immune response, and synaptic regulation. Despite limitations including modest cohort sizes and methodological variability, this integrated approach offers valuable insight into the biological pathways driving AD pathology. Expanding PET-genomic datasets, improving study power, and applying advanced computational tools may further clarify genetic mechanisms and contribute to precision medicine efforts in AD.
正电子发射断层扫描（PET）通过实现体内病理生物标志物的可视化，已成为阿尔茨海默病（AD）研究中的一项强大工具。最近的研究旨在将PET衍生的成像表型与全基因组关联研究（GWAS）相结合，以更好地阐明AD潜在的遗传结构。本系统综述考察了在GWAS背景下利用PET成像（PET-GWAS）来识别与疾病风险、进展和脑区特异性病理相关的基因变异的研究。于2025年2月18日对PubMed和Embase数据库进行了全面检索，共获得210篇文章，其中10篇符合预先定义的纳入标准并被纳入最终综述。纳入标准为研究纳入了AD人群，在GWAS的同时采用了PET成像，并以英文报告了原始全文研究结果。未注册正式方案，且未独立评估偏倚风险。纳入的研究一致确定[此处原文缺失具体基因]为淀粉样蛋白负荷的最强遗传决定因素，同时还揭示了其他重要基因座，包括ABCA7（参与脂质代谢和淀粉样蛋白清除）、[此处原文缺失具体基因]（细胞黏附）、[此处原文缺失具体基因]（免疫反应）、TOMM40（线粒体功能）以及[此处原文缺失具体基因]（在韩国人群中对淀粉样蛋白沉积有保护作用）。纳入的研究表明，PET-GWAS方法可以揭示参与脂质代谢、免疫反应和突触调节等过程的基因座。尽管存在包括样本量适度和方法学变异性等局限性，但这种综合方法为驱动AD病理的生物学途径提供了有价值的见解。扩大PET基因组数据集、提高研究效能以及应用先进的计算工具可能会进一步阐明遗传机制，并有助于AD的精准医学研究。
