The Radiogenomics of Late-onset Alzheimer Disease

Radiogenomics, defined as the integrated analysis of radiologic imaging and genetic data, is a well-established tool shown to augment neuroimaging in the clinical diagnosis, prognostication, and scientific study of late-onset Alzheimer disease (LOAD). Early work using candidate single nucleotide polymorphisms (SNPs) identified genetic variation in APOE, BIN1, CLU, and CR1 as key modifiers of brain structure and function using magnetic resonance imaging (MRI). More recently, polygenic risk scores used in conjunction with MRI and positron emission tomography have shown great promise as a risk-stratification tool for clinical trials and care-management decisions. In addition, recent work using multimodal MRI and positron emission tomography as proxies of LOAD progression has identified novel risk variants that are enhancing our understanding of LOAD pathophysiology and progression. Herein, we highlight key studies and trends in the radiogenomics of LOAD over the past two decades and their implications for clinical practice and scientific research.