Novel Gene Variants That Modify the Risk of Late-Onset Alzheimer's Disease Discovered

A study published in Alzheimer's and Dementia identified 216 novel gene variants that contribute to the risk of developing late-onset Alzheimer's disease by examining carriers of certain genomes that defy their tendency to compound or decrease the likelihood of getting the disorder, reports EurekAlert . "We wanted to test if people who show paradoxical outcomes might have other genetic variants that blunted the risky or protective effects of the APOE genotype they carry," said Baylor College of Medicine Professor Olivier Lichtarge. The researchers used algorithms to compare and contrast the genetic variants present in each subject, in conjunction with a high-throughput fruit fly screen. After discovering the novel gene variants, the team experimentally tested their biological relevance in modifying Alzheimer's disease pathogenesis. "The robotic assays provided us with a quantitative assessment of the actual neuronal impairment," said Baylor's Ismael Al-Ramahi. "We used movement-specific behavioral assays as the main readout of nervous system function. Additionally, we obtained precise information of how variants in each gene modified its physiological function, meaning whether the impact on neuronal function was a result of the gene's under-performance (loss-of-function) or over-performance (gain-of-function). This information is critical for the future development of these biomarkers for therapeutic interventions, either by inhibiting or activating these genes in the future."