MMP-10 and OPN levels improved the differentiation of AD from NDC, and AD from Non-AD, respectively.<h4>Discussion</h4>Our study provides evidence on potential clinical utility of CSF MMP-10 and OPN in diagnosis and supports taking biological aging into consideration in AD research.<h4>Highlights</h4>Elevated osteopontin and matrix metallopeptidase 10 (MMP-10) levels in Alzheimer's disease (AD) cerebrospinal fluid. Here, SPP1 is linked to early-onset autosomal dominant Alzheimer disease.