Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer’s type
Open accessAbstract
Alzheimer’s disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer’s disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer’s type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging. We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n = 410; German DCN, n = 93; German Mannheim, n = 53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer’s type. Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 (MMP-10) showed a higher probability of progressing to dementia of the Alzheimer’s type and a faster cognitive decline. CSF MMP-10 increased the prediction accuracy of CSF amyloid-β 42 (Aβ42), phospho-tau 181 (P-tau181) and total tau (T-tau) for conversion to dementia of the Alzheimer’s type. Including MMP-10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal Aβ42, but normal P-tau181 and T-tau, and in mild cognitive impairment patients with abnormal Aβ42, P-tau181 and T-tau. MMP-10 was correlated with age in subjects with normal Aβ42, P-tau181 and T-tau levels. Our findings support the use of CSF MMP-10 as a prognostic marker for dementia of the Alzheimer’s type and its inclusion in the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of MMP-10 may reflect ageing and neuroinflammation.
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Previous studies found increased levels of CSF MMP-10 in AD, as well as increased rates of disease progression in those with high CSF MMP-10 levels at baseline.
“Regarding the role of MMP‐10 (matrix metalloproteinase 10) in preclinical AD, we note that previous studies found increased levels of CSF MMP‐10 in AD, as well as increased rates of disease progression in those with high CSF MMP‐10 levels at baseline (Martino Adami et al, 2022).”
From The genetic regulation of protein expression in cerebrospinal fluid (2023) · cites this paper as Martino Adami et al, 2022
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The genetic regulation of protein expression in cerebrospinal fluid
Hansson, O., Kumar, A., Janelidze, S., Stomrud, E., Insel, P. S., Blennow, K., Zetterberg, H., Fauman, E., Hedman, Å. K., Nagle, M. W., et al. (2023) · EMBO Molecular Medicine · doi:10.15252/emmm.202216359 · Cited by 56 · see citing works
- Authors
- Martino Adami, P. V., Orellana, A., García, P., Kleineidam, L., Alarcón-Martín, E., Montrreal, L., Aguilera, N., Espinosa, A., Abdelnour, C., Rosende-Roca, M., Pablo Tartari, J., Vargas, L., Mauleón, A., Esteban-De Antonio, E., López-Cuevas, R., Dalmasso, M. C., Campos Martin, R., Parveen, K., Andrade Fuentes, V. M., Amin, N., Ahmad, S., Ikram, M. A., Lewczuk, P., Kornhuber, J., Peters, O., Frölich, L., Rüther, E., Wiltfang, J., Tarraga, L., Boada, M., Maier, W., de Rojas, I., Cano, A., Sanabria, A., Alegret, M., Hernández, I., Marquié, M., Valero, S., van Duijn, C. M., Wagner, M., Jessen, F., Schneider, A., Sáez Goñi, M. E., González Pérez, A., Ruiz, A., & Ramírez, A.
- Affiliations
- Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne , 50937 Cologne , Germany
- Instituto de Salud Carlos III (ES)
- Research Center and Memory Clinic, ACE Alzheimer Center Barcelona, International University of Catalonia , 8029 Barcelona , Spain
- University of Bonn (DE)
- Universitat Internacional de Catalunya (ES)
- University of Cologne (DE)
- University of Oxford (GB)
- Erasmus MC (NL)
- Medical University of Białystok (PL)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Heidelberg University (DE)
- Universitätsmedizin Göttingen (DE)
- German Center for Neurodegenerative Diseases (DE)
- Department of Epidemiology, Erasmus MC , 3015 GD Rotterdam , The Netherlands
- Andalusian Bioinformatics Research Centre (CAEBi) , 41013 Seville , Spain
- ORCID
- Martino Adami, Pamela V
- Orellana, Adelina
- Kleineidam, Luca
- Montrreal, Laura
- Espinosa, Ana
- Vargas, Liliana
- Amin, Najaf
- Ahmad, Shahzad
- Ikram, M Arfan
- Lewczuk, Piotr
- Kornhuber, Johannes
- Peters, Oliver
- Wiltfang, Jens
- Maier, Wolfgang
- Cano, Amanda
- Alegret, Montserrat
- Marquié, Marta
- Valero, Sergi
- van Duijn, Cornelia M
- Wagner, Michael
- Jessen, Frank
- Schneider, Anja
- Ramírez, Alfredo
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-01-27
- Volume
- 145
- Issue
- 7
- Pages
- 2507-2517
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W4210274422
- Cited by
- 46
- References
- 7
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 7 · 2023: 12 · 2022: 2
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- German Federal Ministry of Education and Research (01GI0102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 01GI0434, 01ED2007A)
- European Union’s Horizon 2020 (115975)
- Grifols, Life Molecular Imaging, Araclon Biotech, Alkahest, Laboratorio de análisis Echevarne and IrsiCaixa
- ISCIII (PI13/02434, PI16/01861, PI19/01301)
- Fondo Europeo de Desarrollo Regional
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- matrix metalloproteinase-10, Alzheimer's disease, mild cognitive impairment, subjective cognitive decline, cerebrospinal fluid biomarkers, conversion to dementia, amyloid-beta 42, total tau, cognitive decline, neuroinflammation, aging, disease-modifying therapy
- MeSH terms
- Alzheimer Disease, Humans, Longitudinal Studies, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression, Matrix Metalloproteinase 10, Cognitive Dysfunction
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