Complement dysregulation and Alzheimer's disease in Down syndrome
Aurora Veteleanu1, Sarah Pape2, Kate Davies3
1School of Medicine, UK Dementia Research Institute, Cardiff University, Cardiff, UK.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|September 23, 2022
Summary
Complement levels are dysregulated in Down syndrome (DS), potentially indicating immune issues and Alzheimer's disease (AD) risk. Specific complement changes in DS with AD may help in diagnosis.
Area of Science:
- Immunology
- Neuroscience
- Genetics
Background:
- Down syndrome (DS) is linked to immune dysregulation and increased Alzheimer's disease (AD) risk.
- Complement system dysregulation is implicated in AD neuroinflammation, but its pattern in DS remains unclear.
Purpose of the Study:
- To investigate complement biomarker patterns in adults with DS.
- To determine the relationship between complement dysregulation, APOE genotype, specific SNPs, and dementia in DS.
Main Methods:
- Plasma levels of 14 complement biomarkers were measured in 71 adults with DS and 46 controls.
- Impact of APOE ε4, CLU and CR1 SNPs, and dementia on complement biomarkers was assessed.
Main Results:
- Significant differences in complement activation products, proteins, and regulators were observed between DS and controls.
- Individuals with DS and AD showed decreased C3 and Factor I (FI) compared to those without AD.
- A specific CR1 SNP (rs6656401) was associated with elevated soluble CR1 (sCR1) levels.
Conclusions:
- Complement is dysregulated in DS, reflecting broader immune dysregulation.
- Complement biomarkers may help identify inflammatory events and aid in the diagnosis or prediction of AD in individuals with DS.
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