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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study
Emma L van der Ende1, Carolin Heller2,3, Aitana Sogorb-Esteve2,3
1Alzheimer Center Rotterdam and Department of Neurology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Complement proteins C1q, C3b, C2, and C3 are elevated in symptomatic genetic frontotemporal dementia (FTD) and may increase before symptom onset, suggesting their potential role in disease monitoring.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Neuroinflammation is a key pathological process in frontotemporal dementia (FTD).
- Biomarkers for neuroinflammation in FTD are currently lacking.
- Complement proteins are crucial components of innate immunity.
Purpose of the Study:
- To investigate complement proteins as potential biomarkers in cerebrospinal fluid (CSF) and plasma.
- To assess these biomarkers in presymptomatic and symptomatic genetic FTD mutation carriers.
Main Methods:
- Measured C1q and C3b in CSF using ELISAs in 224 participants (GRN, C9orf72, MAPT mutation carriers and non-carriers).
- Assessed 14 plasma complement proteins using multiplex immunoassays in 431 participants.
- Correlated complement levels with clinical, neuroimaging, NfL, and GFAP data.
Main Results:
- Elevated CSF C1q/C3b and plasma C2/C3 in symptomatic vs. presymptomatic/non-carriers.
- Significant differences observed in C9orf72 mutation carriers.
- Complement proteins correlated with grey matter volume, NfL, GFAP, disease duration, and cognitive scores in presymptomatic and symptomatic carriers.
Conclusions:
- Elevated complement proteins indicate complement activation in symptomatic genetic FTD.
- Complement protein levels may rise before symptom onset, suggesting early involvement.
- While not diagnostic, these proteins may help monitor complement system dysregulation in FTD.
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