Challenges and opportunities in abdominal aortic aneurysm research

AbstractAbdominal Aortic Aneurysms (AAAs) are associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Basic research studies have led to a better understanding of aneurysm disease over the past two decades. There has also been a growing appreciation that fundamental knowledge regarding the process of aneurysmal degeneration is still somewhat limted. Opportunities in research include: 1) the investigation of potential new mechanism-based pharmacologic interventions; 2) identify the genetic basis for an inherited predisposition; 3) develop and refine noninvasive approaches for the early detection; 4) examine potential novel surgical approaches and design new biomaterials; and 5) initiate and promote awareness programs for diagnosis and treatment of aortic aneurysms. The optimal approach to addressing these issues will require integrative, multidisciplinary research programs that involve basic scientists working in concert with vascular and cardiothoracic surgeons, as well as other clinical specialists with expertise in vascular disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele