Adami, Pamela V. Martino, Orellana, Adelina ORCID: 0000-0002-0204-1944, Garcia, Pablo, Kleineidam, Luca, Alarcon-Martin, Emilio, Montrreal, Laura, Aguilera, Nuria, Espinosa, Ana, Abdelnour, Carla, Rosende-Roca, Maitee, Pablo Tartari, Juan, Vargas, Liliana, Mauleon, Ana, Esteban-De Antonio, Ester, Lopez-Cuevas, Rogelio, Dalmasso, Maria Carolina, Martin, Rafael Campos, Parveen, Kayenat, Fuentes, Victor M. Andrade, Amin, Najaf, Ahmad, Shahzad, Ikram, M. Arfan, Lewczuk, Piotr, Kornhuber, Johannes, Peters, Oliver ORCID: 0000-0003-0568-2998, Froelich, Lutz, Ruether, Eckart, Wiltfang, Jens, Tarraga, Lluis, Boada, Merce, Maier, Wolfgang, de Rojas, Itziar, Cano, Amanda ORCID: 0000-0001-9567-4283, Sanabria, Angela, Alegret, Montserrat, Hernandez, Isabel, Marquie, Marta, Valero, Sergi, van Duijn, Cornelia M., Wagner, Michael, Jessen, Frank, Schneider, Anja ORCID: 0000-0001-9540-8700, Saez Goni, Maria Eugenia, Gonzalez Perez, Antonio, Ruiz, Agustin and Ramirez, Alfredo ORCID: 0000-0003-4991-763X (2022). Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer's type. Brain, 145 (7). S. 2507 - 2518. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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Abstract

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-beta 42 (A beta(42)), phospho-tau 181 (P-tau(181)) 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 A beta(42), but normal P-tau(181) and T-tau, and in mild cognitive impairment patients with abnormal A beta(42), P-tau(181) and T-tau. MMP-10 was correlated with age in subjects with normal A beta(42), P-tau(181) 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. Using CSF proteomics in three independent cohorts, Martino-Adami et al. identify matrix metalloproteinase 10 (MMP-10) as a novel CSF prognostic biomarker for dementia of the Alzheimer's type. Adding MMP-10 to existing biomarkers improves their prognostic value in mild cognitive impairment patients with amyloidosis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Adami, Pamela V. MartinoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Orellana, AdelinaUNSPECIFIEDorcid.org/0000-0002-0204-1944UNSPECIFIED
Garcia, PabloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kleineidam, LucaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alarcon-Martin, EmilioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montrreal, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aguilera, NuriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Espinosa, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abdelnour, CarlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosende-Roca, MaiteeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pablo Tartari, JuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vargas, LilianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mauleon, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Esteban-De Antonio, EsterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez-Cuevas, RogelioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dalmasso, Maria CarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, Rafael CamposUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parveen, KayenatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fuentes, Victor M. AndradeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amin, NajafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahmad, ShahzadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ikram, M. ArfanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lewczuk, PiotrUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kornhuber, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, OliverUNSPECIFIEDorcid.org/0000-0003-0568-2998UNSPECIFIED
Froelich, LutzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruether, EckartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiltfang, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tarraga, LluisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boada, MerceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Rojas, ItziarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cano, AmandaUNSPECIFIEDorcid.org/0000-0001-9567-4283UNSPECIFIED
Sanabria, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alegret, MontserratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hernandez, IsabelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marquie, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valero, SergiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Duijn, Cornelia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, AnjaUNSPECIFIEDorcid.org/0000-0001-9540-8700UNSPECIFIED
Saez Goni, Maria EugeniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez Perez, AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruiz, AgustinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
URN: urn:nbn:de:hbz:38-695867
DOI: 10.1093/brain/awac024
Journal or Publication Title: Brain
Volume: 145
Number: 7
Page Range: S. 2507 - 2518
Date: 2022
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2156
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MILD COGNITIVE IMPAIRMENT; DISEASE; SENESCENCE; DIAGNOSIS; FRAMEWORK; MMP-9Multiple languages
Clinical Neurology; NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69586

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