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Published on: September 3, 2021
Altered TIMP-3 Levels in the Cerebrospinal Fluid and Plasma of Patients with Alzheimer's Disease
Jung Hyun Park1, Sun-Jung Cho1, Chulman Jo1
1Department of Chronic Disease Convergence Research, Division of Brain Disease Research, Korea National Institute of Health, 187 Osongsaengmyeong2-ro, Osong-eup, Heungdeok-gu, Cheongju-si 28159, Korea.
Abstract:
Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment and is suggested to play an indirect role in regulating Aβ production and the pathophysiology of Aβ deposition in brains. However, studies on the amount of TIMP-3 in bodily fluids of Alzheimer's disease (AD) patients have not been conducted. Here, we investigated the relationship between fluid TIMP-3 levels and AD pathology. We first showed that the fluid levels of TIMP-3 were lower in AD dementia patients compared with in non-AD patients. ELISA results revealed that plasma levels of TIMP-3 in 65 patients with AD were significantly lower than those in 115 healthy control subjects and 71 mild cognitive impairment (MCI) subjects. Furthermore, we found that cerebrospinal fluid (CSF) level of TIMP-3 was decreased in AD compared with that in healthy control. These data suggest that fluid TIMP-3 levels negatively correlated with progress of cognitive decline. Collectively, our study suggests that alterations of fluid TIMP-3 levels might be associated with AD pathology.
Insights
Fluid levels of Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) are lower in Alzheimer's disease (AD) patients. Lower TIMP-3 levels correlate with cognitive decline, suggesting a link to AD pathology.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) is an extracellular component.
- TIMP-3 may indirectly influence amyloid-beta (Aβ) production and deposition in Alzheimer's disease (AD).
- Previous studies have not examined fluid TIMP-3 levels in AD patients.
Purpose of the Study:
- To investigate the association between fluid TIMP-3 levels and AD pathology.
- To determine if TIMP-3 levels differ in bodily fluids of AD patients compared to non-AD individuals.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma TIMP-3 levels.
- Cerebrospinal fluid (CSF) TIMP-3 levels were also analyzed.
- Patient groups included AD dementia, mild cognitive impairment (MCI), and healthy controls.
Main Results:
- Plasma TIMP-3 levels were significantly lower in AD patients compared to healthy controls and MCI subjects.
- Cerebrospinal fluid (CSF) TIMP-3 levels were decreased in AD patients relative to healthy controls.
- Fluid TIMP-3 levels showed a negative correlation with the progression of cognitive decline.
Conclusions:
- Reduced fluid TIMP-3 levels are associated with Alzheimer's disease pathology.
- Altered TIMP-3 levels in bodily fluids may serve as a potential biomarker for AD.
- These findings highlight a potential role for TIMP-3 in AD pathogenesis.
