However, Spp1 is notably upregulated in pathological conditions, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis [51, 52, 53], as well as acute brain injuries like stroke and hypoxic–ischemic injury [53, 54, 55]. This evidence concerns the gene SPP1 and early-onset autosomal dominant Alzheimer disease.