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

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Abstract

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 disease (Non-AD) individuals to evaluate their clinical utility.

METHODS

We included 137 participants (37 NDC, 67 AD, 33 Non-AD) from the UCL Dementia Research Centre and measured matrix metallopeptidase 10 (MMP-10), osteopontin (OPN), neurofilament-light, and glial fibrillary acidic protein in cerebrospinal fluid (CSF) samples 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 CSF 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 AD diagnosis and supports taking biological aging into consideration in AD research.

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