Understanding mechanisms and seeking cures for Alzheimer's disease: why we must be "extraordinarily diverse".

After more than a century since Dr. Alois Alzheimer first described the pathological hallmarks accompanying the defining clinical features of the disease, we have yet to deliver any meaningful disease-modifying treatments to our patients. In this article, I present a rationale for the need to be "extraordinarily diverse" in seeking effective ways to treat or prevent this devastating disease. This approach is based on applying a systems-biology perspective at the population level, using a diverse array of "OMICS" methodologies to identify molecular mechanisms associated with well-established AD risk factors including systemic inflammation, obesity, and insulin resistance. We believe that applying this strategy to understand longitudinal changes in human physiology during aging is of paramount importance in identifying meaningful opportunities to intervene effectively in AD.