Sex-specific associations of matrix metalloproteinases in Alzheimer's disease.
Alzheimer disease
Biomarkers
Cerebrospinal fluid
Cognitive decline
Matrix metalloproteinases
Neurodegenerative diseases
Prognosis
Sex differences
Tissue inhibitor of metalloproteinases
Journal
Biology of sex differences
ISSN: 2042-6410
Titre abrégé: Biol Sex Differ
Pays: England
ID NLM: 101548963
Informations de publication
Date de publication:
23 05 2023
23 05 2023
Historique:
received:
19
09
2022
accepted:
21
04
2023
medline:
25
5
2023
pubmed:
24
5
2023
entrez:
24
5
2023
Statut:
epublish
Résumé
Alzheimer's disease (AD) can be characterised in vivo by biomarkers reflecting amyloid-β (Aβ) and tau pathology. However, there is a need for biomarkers reflecting additional pathological pathways. Matrix metalloproteinases (MMPs) have recently been highlighted as candidate biomarkers for sex-specific mechanisms and progression in AD. In this cross-sectional study, we investigated nine MMPs and four tissue inhibitors of metalloproteinases (TIMPs) in the cerebrospinal fluid of 256 memory clinic patients with mild cognitive impairment or dementia due to AD and 100 cognitively unimpaired age-matched controls. We studied group differences in MMP/TIMP levels and examined the associations with established markers of Aβ and tau pathology as well as disease progression. Further, we studied sex-specific interactions. MMP-10 and TIMP-2 levels differed significantly between the memory clinic patients and the cognitively unimpaired controls. Furthermore, MMP- and TIMP-levels were generally strongly associated with tau biomarkers, whereas only MMP-3 and TIMP-4 were associated with Aβ biomarkers; these associations were sex-specific. In terms of progression, we found a trend towards higher MMP-10 at baseline predicting more cognitive and functional decline over time exclusively in women. Our results support the use of MMPs/TIMPs as markers of sex differences and progression in AD. Our findings show sex-specific effects of MMP-3 and TIMP-4 on amyloid pathology. Further, this study highlights that the sex-specific effects of MMP-10 on cognitive and functional decline should be studied further if MMP-10 is to be used as a prognostic biomarker for AD.
Identifiants
pubmed: 37221606
doi: 10.1186/s13293-023-00514-x
pii: 10.1186/s13293-023-00514-x
pmc: PMC10207710
doi:
Substances chimiques
Matrix Metalloproteinase 10
EC 3.4.24.22
Matrix Metalloproteinase 3
EC 3.4.24.17
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
35Informations de copyright
© 2023. The Author(s).
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