Investigating the Neuroimmune Component of Alzheimer's disease in African-Americans

Background According to the 2021 Alzheimer's Association Facts and Figures report, older blacks/African Americans are twice as likely to have Alzheimer's or other dementia than older whites. However, the biology by which older blacks/African Americans may be more likely to have Alzheimer's or other dementia than older whites is not yet clear. Microglia are the primary immune cells of the brain and help maintain healthy nerve cells. Microglia sense and help remove proteins that can accumulate in the brain in Alzheimer's and other brain diseases and that may contribute to some of the nerve cell damage in these diseases. In Alzheimer's, past research has suggested that microglia become overactivated, which can cause inflammation in the brain that may also damage nerve cells. Studies show that microglia are very 'plastic' cells and can exist in different forms. During aging, microglia can enter a form that could be directly damaging to nerve cells. Research suggests that beneficial and potentially harmful microglia may coexist in the aged brain. Studies also reveal that social and environmental factors and stressors experienced by a person throughout their life may impact microglia. Dr. Marta Olah has developed a new biochemical technique that can study different forms of individual live microglia and other immune cells from human brain tissue. Dr. Olah and colleagues have used this technique to study microglia from brain tissue of older whites. Research Plan Building on preliminary results, Dr. Olah and colleagues will use their new technique to study the different forms of microglia found in tissue samples from older blacks/African Americans with Alzheimer's and cognitively unimpaired older blacks/African Americans. The researchers will collect data about the size and shape of the microglia and study which genes may be turned 'on' or 'off' in different forms of microglia. The researchers will compare their findings from older blacks/African Americans with Alzheimer's to cognitively unimpaired blacks/African Americans. Finally, Dr. Olah's team will compare these results to their initial findings in older whites. Impact If successful, the study results could expand our knowledge about the impact of the structure and forms of microglia on brain changes in older blacks/African Americans with Alzheimer's. The study could also help address disparities in Alzheimer's and other dementia research. The results could inform our understanding of why older blacks/African Americans may be more likely to have Alzheimer's than older whites and could help develop potential therapies to prevent or slow down the progression of disease in older blacks/African Americans.