Research

Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer's disease

Erik Stomrud¹²*, Maria Björkqvist³, Sabina Janciauskiene⁴, Lennart Minthon¹² and Oskar Hansson¹²*

• * Correponding authors: Erik Stomrud erik.stomrud@med.lu.se - Oskar Hansson oskar.hansson@med.lu.se

Author Affiliations

¹ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University; SUS, 205 02 Malmö, Sweden

² Neuropsychiatric Clinic, Skåne University Hospital; 205 02 Malmö, Sweden

³ Neuronal Survival Unit, Department of Experimental Medical Science, Lund University; Wallenberg Neuroscience Center, BMC A10, Sölvegatan 17, Lund, Sweden

⁴ Wallenberg Laboratory, Department of Clinical Sciences Malmö, Lund University; SUS, 205 02 Malmö, Sweden

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Alzheimer's Research & Therapy 2010, 2:20 doi:10.1186/alzrt44

Published: 24 June 2010

Abstract

Introduction

Matrix metalloproteinases (MMP) are believed to be involved in the pathologic processes behind Alzheimer's disease (AD). In this study, we aimed to examine the cerebrospinal fluid (CSF) levels of MMPs and tissue inhibitors of metalloproteinase-1 (TIMP-1) in individuals with AD dementia and cognitively healthy elderly individuals, and to investigate their relationship with established CSF biomarkers for Alzheimer's disease.

Methods

CSF was collected from 38 individuals with AD dementia and 34 cognitively healthy elderly individuals. The CSF was analyzed for MMP-1, MMP-3, MMP-9, TIMP-1, β-amyloid_1-42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau). MMP/TIMP-1 ratios were calculated. APOE genotype was determined for the participants.

Results

AD patients had higher MMP-9/TIMP-1 ratios and lower TIMP-1 levels compared to cognitively healthy individuals. In AD patients, the MMP-9/TIMP-1 ratio correlated with CSF T-tau, a marker of neurodegeneration. Interestingly, the cognitively healthy individuals with risk markers for future AD, i.e. AD-supportive CSF biomarker levels of T-tau, P-tau and Aβ42 or the presence of the APOE ε4 allele, had higher CSF MMP-3 and MMP-9 levels and higher CSF MMP-3/TIMP-1 ratios compared to the healthy individuals without risk markers. The CSF levels of MMP-3 and -9 in the control group also correlated with the CSF T-tau and P-tau levels.

Conclusions

This study indicates that MMP-3 and MMP-9 might be involved in early pathogenesis of AD and that MMPs could be associated with neuronal degeneration and formation of neurofibrillary tangles even prior to development of overt cognitive dysfunction.