SPP1 and early-onset autosomal dominant Alzheimer disease: In an earlier study, Simonsen et al. employed proteomic analysis of cerebrospinal fluid samples and found elevated levels of a phosphorylated C-terminal fragment of osteopontin in mild cognitive-impaired patients who progressed to Alzheimer disease compared to those who stayed stable over the 4–6 years of follow-up, and healthy controls [224].