Increase in Matrix Metaloproteinase‐10 is associated with tau, neurodegeneration and reduced brain perfusion in the right temporal lobe

Abstract

AbstractBackgroundBlood brain barrier dysfunction amplifies neuroinflammation, which may drive Alzheimer’s Dementia (AD) pathology. Regional cerebral blood flow (RCBF), measured by HMPAO SPECT, is an established biomarker for AD diagnosis. Matrix Metalloproteinase‐10 (MMP‐10), an enzyme involved in blood brain barrier function through regulating the breakdown of extracellular matrix, was recently proposed as a biomarker of progression to AD. In this study, we examine the relationship between RCBF and levels of MMP‐10 in the cerebrospinal fluid (CSF).Materials and MethodsDatasets of 91 participants from a heterogenous clinical cohort, investigated for dementia due to cognitive complaints were analysed. CSF levels of MMP‐10 were measured using the OLINK proximity extension array platform. HMPAO SPECT scans were analysed using Statistical Parametric Mapping (SPM). A univariate linear regression model was used in SPM to quantify the impact of MMP‐10 changes on brain perfusion.ResultsSPM results showed that higher levels of MMP‐10 in CSF are associated with significant reduction in RCBF (family‐wise error corrected p<0.05). The neuroimaging signature of changes in RCBF with increasing MMP‐10 is outlined in Figure 1. The main cluster of reduction in perfusion is on the right temporal lobe with an additional cluster on the right medial frontal lobe.ConclusionIncreased levels of MMP‐10 in CSF have been associated with blood brain barrier vulnerability and faster cognitive decline in AD. Here we identified a right sided neuroimaging signature in RCBF with increasing levels MMP‐10. This may indicate that by the time of symptoms onset the right side is the fastest progressing as it is catching up with the left side. Right sided changes have been previously associated with delusions, disinhibition and irritability in AD and linked with increased carer burden. The significant reduction in RCBF of the right temporal lobe identified in our study, further reinforces a role for MMP‐10 as a marker of progression to AD.Acknowledgement: Dr Sofia Michopoulou, is funded through an Integrated Clinical Academic Lectureship by Health Education England (HEE) / NIHR for this research project (NIHR301287). The views expressed in this publication are those of the authors.