Aging‐related matrix metallopeptidase 10 and osteopontin levels are associated with pathology, cognitive decline, and age at onset in Alzheimer's disease

INTRODUCTION: Aging is the strongest risk factor for Alzheimer's disease (AD) characterized by amyloid-β (Aβ) plaques and tau tangles in the brain. We aim to compare biological aging-related biomarkers among AD, non-neurodegenerative control (NDC) and non-AD neurodegenerative (Non-AD) individuals to evaluate their clinical utility. METHODS: We included 137 participants (37 NDC, 67 AD, 33 Non-AD) from the University College London (UCL) Dementia Research Centre and measured matrix metallopeptidase 10 (MMP-10), osteopontin (OPN), neurofilament-light, and glial fibrillary acidic protein in cerebrospinal fluid (CSF) in addition to Aβ/pTau and clinical parameters. RESULTS: Elevated MMP-10 associated with poorer cognition and later onset specifically in AD, whereas elevated OPN associated with Aβ and tau pathology. MMP-10 and OPN levels improved the differentiation of AD from NDC, and AD from Non-AD, respectively. DISCUSSION: 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. HIGHLIGHTS: Elevated osteopontin and matrix metallopeptidase 10 (MMP-10) levels in Alzheimer's disease (AD) cerebrospinal fluid. MMP-10 levels are linked to age at onset and cognitive decline. Osteopontin levels are linked to AD pathologies in the cerebrospinal fluid. MMP-10 levels improved discrimination of AD from non-neurodegenerative controls. Osteopontin levels improved discrimination of AD from other neurodegenerative cases.