Principal Investigator: Dr Sandra Barral
Columbia University, New York, USATags: 50442, genome-wide gene-based analyses, late onset alzheimer’s disease, longitudinally trajectories, traumatic brain injury
Scientific rationale. There is a significant deficit in the literature investigating the possible association between traumatic brain injury and increased susceptibility to develop Alzheimer’s disease later in life. Some studies have shown that patients with Alzheimer’s disease had a significantly greater incidence of history of head trauma while others report were unable to confirm this association. It is highly likely that traumatic brain injury influences the aging process producing adverse clinical consequences, such as permanent neurological deficits among others. Genetic variation has been investigated as a potential modulator of the development of Alzheimer’s disease after traumatic brain injury; however, no specific genes have been discovered.
Aims. This proposal we will explore the interaction of genetic risk factors with traumatic brain injury in predicting the risk of Alzheimer’s disease. Using longitudinal data from two different cohorts we will characterize the memory trajectories in four different groups of subjects: group 1) subjects with both Alzheimer’s disease and traumatic brain injury, group 2) subjects with Alzheimer’s disease but not traumatic brain injury, group 3) subjects with traumatic brain injury but not Alzheimer’s disease and group 4) subjects without Alzheimer’s disease and without traumatic brain injury. We will then test genome-wide the interaction of all genes with traumatic brain injury in predicting risk of Alzheimer’s disease.
Project duration. We anticipate the project will be complete in a year (Spring 2020).
Public health impact. A better understanding of the complex genetic pathways underlying traumatic brain injury and Alzheimer’s disease can have significant implications in the clinical management of these patients. Identifying individuals at higher risk of developing Alzheimer’s disease after traumatic brain injury (carriers of the identified high-risk genetic variants), will aid the prognosis and early detection of disease and subsequent therapeutic decisions. Risk prediction can be personalized using the genetic profile of the subject, which may maximize the likelihood of successfully pharmacological interventions. The therapeutic strategies can be designed more effectively, since carriers of the risk variant will have a treatment tailored to their genetic profile.