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.