Evaluation of SORL1 in Lewy Body Dementia Identifies No Significant Associations

Lewy body dementia (LBD) is a clinically heterogeneous neurodegenerative disorder characterized by parkinsonism, visual hallucinations, fluctuating mental status, and rapid eye movement sleep behavior disorder. LBD lies along a spectrum between Parkinson's disease and Alzheimer's disease, and recent evidence suggests that the genetic architectures of these age-related syndromes are intersecting. In summary, we did not find a significant enrichment of rare, damaging SORL1 mutations in our well-powered LBD cohort. Our data set is, to our knowledge, the largest genome-sequence cohort in this understudied disease. Although it is possible that an association was missed due to allelic heterogeneity, our findings indicate that caution should be exercised when interpreting SORL1 mutations in LBD, as the current evidence does not conclusively support an association with disease risk.