Researchers found that damage to the SORL1 gene in Alzheimer’s Disease patients results in a decrease of two key proteins critical for healthy neurons. Their findings, using stem-cell-based techniques, suggest potential alternative treatments for AD, especially for patients unresponsive to current therapies.
Historically, researchers have studied three potent genetic drivers of AD , which are commonly mutated in hereditary, early-onset AD . Preclinical models and cell-based systems largely rely on mutations in these genes to model AD, even though in many people with late-onset AD, a more complex interaction between genes, lifestyle, and environment determines the presentation of AD.
Without APOE and CLU, neurons cannot properly regulate lipids, which accumulate in droplets that may impair neurons’ abilities to communicate with each other. The researchers verified their lab-based results by examining natural genetic variation inexpression in the brain tissue of 50 members of the cohorts, finding again that lower SORL1 activity in neurons was correlated with reduced APOE and CLU in these people.