Alzheimer’s disease research is increasingly focused on neuroinflammation because changes in the brain’s immune system, especially in support cells called microglia and astrocytes, are now believed to play an important role in disease risk and progression. At the same time, current blood tests for inflammation are often too broad and cannot clearly distinguish Alzheimer’s-related changes from inflammation elsewhere in the body. This project will improve blood-based biomarker development by identifying the specific molecular forms of two promising proteins, GFAP and osteopontin (OPN/SPP1), that are most informative for Alzheimer’s disease and related dementias. Rather than measuring only the total amount of these proteins, we will use advanced antibody-based methods and high-resolution mass spectrometry to determine which proteoforms provide the strongest and most useful signal in blood. By the end of the project, we expect to deliver a short list of the most promising blood-accessible biomarker candidates for future assay development, clinical studies, and drug trials aimed at improving diagnosis and treatment monitoring in Alzheimer’s disease.