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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
Published on: January 28, 2014
Biomarkers
Feng Gao1, Yaxi Zhan2, Yong Shen3
1Department of Neurology, Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Background:
Amyloid and cerebrovascular pathologies play critical role in the pathogenesis of Alzheimer's disease (AD). Matrix metalloproteinases (MMPs) is known to degrade Aβ peptides, while they also contribute to cerebrovascular pathology. Presently, the precise roles of MMPs in AD remain unclear. Therefore, we investigated relationships between CSF levels of MMPs and amyloid and cerebrovascular pathologies.
Method:
A total of 299 participants were included from the CANDI cohort, including 50 cognitively unimpaired (CU) individuals, 69 patients with MCI, 137 AD patients, and 43 non-ADD patients. MMP2, MMP9, Aβ38, Aβ40 and Aβ42 were measured in the CSF. Participants underwent structural MRI and AV45 PET scan. And fluid biomarkers (Qalb and CSF PDGFRβ) were used to assess cerebrovascular pathologies.
Result:
CSF MMP2 levels in MCI and AD patients were significantly lower compared to CU individuals and non-ADD patients. Decreased CSF MMP2 levels, but not MMP9 were associated with lower levels of CSF Aβ peptides (Aβ38, Aβ40, Aβ42) and higher Aβ PET SUVR. Notably, CSF MMP2 was positively associated with multiple cortical regions within the AD continuum, but not in the non-ADD continuum. Meanwhile, we observed positive correlations between CSF MMP2 and MMP9 with cerebrovascular pathologies, including WMH volume, CMB, lacunes, PVS, and Qalb. Additionally, lower CSF MMP2 was associated with longitudinal brain atrophy.
Conclusion:
This study suggested the involvement of MMPs in the cerebrovascular damage and the protective role of MMP2 in amyloid pathology, which highlight that the clinical application of MMP inhibitors should consider the protective effect of MMP2 on amyloid pathology.
Insights
Matrix metalloproteinases (MMPs) like MMP2 may protect against amyloid pathology in Alzheimer's disease (AD). Lower MMP2 levels correlate with increased amyloid and cerebrovascular damage in AD patients.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Alzheimer's disease (AD) pathogenesis involves amyloid and cerebrovascular issues.
- Matrix metalloproteinases (MMPs) influence both amyloid-beta (Aβ) degradation and cerebrovascular pathology.
- The exact role of MMPs in AD remains unclear, necessitating further investigation.
Purpose of the Study:
- To investigate the relationships between cerebrospinal fluid (CSF) levels of MMPs and amyloid and cerebrovascular pathologies in AD.
- To clarify the specific roles of MMP2 and MMP9 in the context of AD progression.
Main Methods:
- Analysis of CSF samples from 299 participants (cognitively unimpaired, MCI, AD, non-AD) from the CANDI cohort.
- Measurement of CSF MMP2, MMP9, Aβ38, Aβ40, and Aβ42.
- Utilized structural MRI, AV45 PET scans, and fluid biomarkers (Qalb, CSF PDGFRβ) to assess pathologies.
Main Results:
- CSF MMP2 levels were significantly lower in MCI and AD patients compared to controls.
- Decreased MMP2, not MMP9, correlated with lower CSF Aβ levels and higher Aβ PET SUVR.
- CSF MMP2 and MMP9 positively correlated with cerebrovascular pathologies (WMH, CMB, lacunes, PVS, Qalb).
- Lower CSF MMP2 was associated with longitudinal brain atrophy.
Conclusions:
- MMPs are implicated in cerebrovascular damage.
- MMP2 appears to have a protective role against amyloid pathology in AD.
- Clinical use of MMP inhibitors in AD should account for MMP2's protective effects on amyloid pathology.
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