Abstract
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 APOE as the strongest genetic determinant of amyloid burden, while revealing additional significant loci including ABCA7 (involved in lipid metabolism and amyloid clearance), FERMT2 (cell adhesion), CR1 (immune response), TOMM40 (mitochondrial function), and FGL2 (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.