title: A neprilysin polymorphism and amyloid-beta plaques after traumatic brain injury.
abstract: Traumatic brain injury (TBI) induces the rapid formation of Alzheimer's disease (AD)-like amyloid-beta (AB) plaques in about 30% of patients. However, the mechanisms behind this selective plaque formation are unclear. We investigated a potential association between amyloid deposition acutely after TBI and a genetic polymorphism of the AB-degrading enzyme, neprilysin (n = 81). We found that the length of the GT repeats in AB-accumulators was longer than in non-accumulators. Specifically, there was an increased risk of AB plaques for patients with more than 41 total repeats (p < 0.0001; OR: 10.1). In addition, the presence of 22 repeats in at least one allele was independently associated with plaque deposition (p = 0.03; OR: 5.2). In contrast, the presence of 20 GT repeats in one allele was independently associated with a reduced incidence of AB deposition (p = 0.003). These data suggest a genetically linked mechanism that determines which TBI patients will rapidly form AB plaques. Moreover, these findings provide a potential genetic screening test for individuals at high risk of TBI, such as participants in contact sports and military personnel.
authors.affiliation: Penn Center for Brain Injury and Repair, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Johnson
authors.forename: William
authors.initials: W
authors.lastname: Stewart
authors.forename: David I
authors.initials: DI
authors.lastname: Graham
authors.forename: Janice E
authors.initials: JE
authors.lastname: Stewart
authors.forename: Amy H
authors.initials: AH
authors.lastname: Praestgaard
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Smith