Genetic Complexity of Early-Onset Alzheimer’s Disease

The recent advances in “omics” technologies (e.g., next-generation sequencing) have made the precision medicine possible. Knowledge about genetics of Alzheimer’s disease (AD), the most prevalent form of dementia, is important to manage the challenges of aging populations. So far, genetic analyses of families with autosomal dominant AD, presenting with early-onset dementia (<65 years of age), have found three causal genes: APP, PSEN1, and PSEN2. Genetics is now widely applied to AD diagnosis, monitoring, and the search for a potential treatment. The ability to detect carriers of causal mutations could help to evaluate the efficacy of AD therapies in the longitudinal clinical trials of the individuals at either pre-symptomatic or early stages of dementia. We provide an overview for the molecular genetic findings available for early-onset AD; discuss how this knowledge can be applied in clinical practice and highlight strategies to detect novel AD genes.