Increase in Matrix Metaloproteinase‐10 is associated with tau, neurodegeneration and reduced brain perfusion in the right temporal lobe
Increase in Matrix Metaloproteinase‐10 is associated with tau, neurodegeneration and reduced brain perfusion in the right temporal lobe
Background: blood 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 methods: datasets 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.
Results: SPM results showed that higher levels of MMP-10 in CSF are associated with significant reduction in RCBF (family-wise error corrected p
Conclusion: increased 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.
Michopoulou, Sofia
888207f0-a8b6-4ecb-ae0c-ad03d2128a2d
Prosser, Angus
de1efee5-67f5-478e-8cfa-12a8e78a68e5
Dickson, John
627f7f54-97e9-4cc1-812c-728c3973265d
Guy, Matt J.
1a40b2ed-3aec-4fce-9954-396840471c28
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Kipps, Christopher
e43be016-2dc2-45e6-9a02-ab2a0e0208d5
1 December 2023
Michopoulou, Sofia
888207f0-a8b6-4ecb-ae0c-ad03d2128a2d
Prosser, Angus
de1efee5-67f5-478e-8cfa-12a8e78a68e5
Dickson, John
627f7f54-97e9-4cc1-812c-728c3973265d
Guy, Matt J.
1a40b2ed-3aec-4fce-9954-396840471c28
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Kipps, Christopher
e43be016-2dc2-45e6-9a02-ab2a0e0208d5
Michopoulou, Sofia, Prosser, Angus, Dickson, John, Guy, Matt J., Teeling, Jessica and Kipps, Christopher
(2023)
Increase in Matrix Metaloproteinase‐10 is associated with tau, neurodegeneration and reduced brain perfusion in the right temporal lobe.
Alzheimer's & Dementia, 19 (S14), [e072100].
(doi:10.1002/alz.072100).
Abstract
Background: blood 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 methods: datasets 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.
Results: SPM results showed that higher levels of MMP-10 in CSF are associated with significant reduction in RCBF (family-wise error corrected p
Conclusion: increased 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.
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Published date: 1 December 2023
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Local EPrints ID: 486252
URI: http://eprints.soton.ac.uk/id/eprint/486252
ISSN: 1552-5260
PURE UUID: c163bfb0-9677-4252-8414-e0a467e315dc
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Date deposited: 16 Jan 2024 17:31
Last modified: 14 Dec 2024 03:15
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Author:
Sofia Michopoulou
Author:
John Dickson
Author:
Matt J. Guy
Author:
Christopher Kipps
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