Sex-specific associations of matrix metalloproteinases in Alzheimer’s disease

Biology of Sex Differences

Research

Trine H. Edwin¹  Anne-Brita Knapskog¹  Mari Aksnes²  Nathalie B. Halaas³  Marius Myrstad⁴  Farrukh A. Chaudhry⁵  Rannveig S. Eldholm⁶  Ingvild Saltvedt⁶  Leiv O. Watne⁷ 

[1] Department of Geriatric Medicine, Oslo University Hospital, 0450, Oslo, Norway;Department of Geriatric Medicine, University of Oslo, 0315, Oslo, Norway;Department of Geriatric Medicine, University of Oslo, 0315, Oslo, Norway;Department of Geriatric Medicine, Oslo University Hospital, 0450, Oslo, Norway;Department of Internal Medicine, Bærum Hospital, Vestre Viken Hospital Trust, 1346, Gjettum, Norway;Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, 1346, Gjettum, Norway;Department of Molecular Medicine, University of Oslo, 0315, Oslo, Norway;Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, 7030, Trondheim, Norway;Department of Geriatric Medicine, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, 7030, Trondheim, Norway;Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway;Department of Geriatric Medicine, Akershus University Hospital, Lørenskog, Norway;

关键词: Alzheimer disease;    Biomarkers;    Cerebrospinal fluid;    Cognitive decline;    Matrix metalloproteinases;    Neurodegenerative diseases;    Prognosis;    Sex differences;    Tissue inhibitor of metalloproteinases;   

DOI  :  10.1186/s13293-023-00514-x

 received in 2022-09-19, accepted in 2023-04-21,  发布年份 2023

来源: Springer

【 摘 要 】

IntroductionAlzheimer’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.MethodsIn 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.ResultsMMP-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.ConclusionOur 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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Fig. 5