SPP1 and early-onset autosomal dominant Alzheimer disease: There is evidence for both local and systemic sources of OPN based on studies of a variety of tissues and cells including macrophages, activated microglia, astrocytes and epithelial cells33,87–92, as well as neurodegenerative diseases such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and ischemic stroke53,91,93–97.