Identifying Aging and AD-Related Protein Changes in Skin Cells, Blood and Spinal Fluid That Can Be Used as Markers of Disease or Therapeutic Targets

Age is the strongest risk factor for Alzheimer’s disease (AD) and the wrinkling of our skin. This study will investigate a link between aging and AD-related changes in the skin and the brain. The ultimate goal of the project is to identify new treatment approaches and new markers of aging and AD in the skin, blood and/or spinal fluid.

The goal of my project is to determine if aging tissues (like skin) generate signals that may drive neurodegeneration and aging in the human brain. We know that skin demonstrates highly visible signs of aging and that skin cells can release various growth factors and inflammatory signals. For this study, I will use existing skin cells from my cell bio-repository and also collect additional samples from research volunteers in the Emory Goizueta Alzheimer’s Disease Research Center. In Aim 1, I will identify the unique changes that aging and Alzheimer’s disease imprints on skin cells. In particular, we will be looking at different cell pathways as well as how cells process proteins, especially in aging and Alzheimer’s disease. In Aim 2, I will look specifically at the signals released from these skin cells and correlate those findings with signals that we see in blood and cerebrospinal fluid from both aging and Alzheimer’s disease research subjects. This will allow us to clarify how skin cell signals may travel in the human body. I will use standard biochemical and cell culture methods as well as more sophisticated protein sequencing to identify these changes. Preliminary findings demonstrated that aging can indeed alter how these cells function, however little is known about which systemic tissues, like skin, influence cells in the brain. Understanding this dynamic is critical because it may help us identify novel biomarkers of aging and Alzheimer’s disease. Perhaps more intriguing, is that findings may also identify novel therapeutic approaches to treat the negative effects from aging and Alzheimer’s disease, either by reducing negative signals from skin or augmenting the positive signals. Also of importance is that skin, the largest organ in the human body, is highly accessible for manipulating these signals, unlike the brain which is protected by the blood brain barrier. Overall, I am hopeful that this project will generate novel insights into cellular mechanisms that contribute aging and Alzheimer’s disease. The identification of biomarkers as well as novel therapeutics approaches could also have lasting effects on how we identify patients, how we monitor for therapeutic efficacy and how we manage aging and Alzheimer’s disease.