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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
Published on: January 28, 2014
Biomarkers
Julia Loncke1,2, Cynthia Picard2, Henrik Zetterberg3,4
1Integrated Program in Neuroscience, Faculty of Medicine and Health Science, McGill University, Montréal, QC, Canada.
Complement system activation is linked to tau pathology and synaptic changes in individuals at high risk for Alzheimer's disease (AD). These findings mirror patterns seen in mild cognitive impairment (MCI) and AD stages.
Area of Science:
- Neuroimmunology
- Neurodegenerative Diseases
- Alzheimer's Disease Pathogenesis
Background:
- The complement system plays a role in synaptic pruning, but its dysregulation is implicated in Alzheimer's disease (AD) pathogenesis.
- Elevated complement proteins in cerebrospinal fluid (CSF) are observed in AD patients, yet its role in pre-symptomatic and later stages remains unclear.
Purpose of the Study:
- To investigate the relationship between complement system proteins and AD biomarkers in individuals with a familial risk for AD.
- To explore the association of complement levels with synaptic integrity and cognitive function in pre-symptomatic and symptomatic AD stages.
Main Methods:
- CSF samples from the PREVENT-AD cohort (familial AD risk) and ADNI cohort (cognitively normal, MCI, AD) were analyzed for complement proteins (C1q, C3, C3b, Factor H) and AD biomarkers (Aβ42, pTau181, total tau).
- Proteomic analysis (SomaScan, OLINK PEA) and mass spectrometry were used to assess complement and synaptic marker (GAP43, SNAP25, SYT1, ADAM22, ADAM23) levels.
- Cognitive function was evaluated using the RBANS scale.
Main Results:
- Significant positive associations were found between tau pathology markers (pTau181, total tau) and complement proteins (C1q, Factor H) in the PREVENT-AD cohort, irrespective of sex and APOE4 status.
- These complement-tau associations mirrored those observed in MCI and AD patients within the ADNI cohort.
- Complement proteins C1q and Factor H were positively associated with synaptic proteins (GAP43, SNAP25, SYT1, ADAM23) but not cognitive performance in PREVENT-AD participants.
Conclusions:
- A clear link exists between complement system activation, tau pathology, and synaptic integrity in asymptomatic individuals with familial AD risk.
- The observed complement patterns in at-risk individuals resemble those found in mild cognitive impairment (MCI) and AD.
- Further research involving volumetric MRI and PET imaging is underway to complement these findings.
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