Objective: To estimate levels of complement factor H (CFAH), phosphorylated alpha-syn (p- a-syn), gelsolin, carnosine dipeptidase-1 (CNDP1) and DKK3 in serum of Parkinson’s disease (PD) patients to understand their role in pathogenesis.
Background: Our earlier CSF-based investigations showed fibrinogen (FIB), to be a putative biomarker for PD and PD with cognitive impairment (PDCI). It was also upregulated in serum, suggesting seamless communication between body fluids and serum as an ideal biofluid. CSF-based proteomics also showed involvement of CFAH, gelsolin, CNDP-1 and DKK3, however, their role in PD is not known. If quantifiable in serum, it would be a conclusive step for biomarker validation.
Method: Following the diagnosis of PD by neurologists (Dept. of Neurology, NIMHANS), blood samples were collected and serum was isolated (n=24) for ELISA-based estimations, using commercially available kits. 16 age and sex-matched controls were also recruited. We further studied 5μ formalin-fixed paraffin-embedded striatal sections from normally aged donor subjects and PD patients. Immunofluorescence-based staining was performed to study the CFAH-labeled profiles.
Results: The levels of the selected proteins were significantly higher in patient serum vis-à-vis the controls (CFAH ***p<0.001; p-a-Syn *p<0.0246; CNDP1 ****p<0.0001; DKK3 ***p<0.01 and Gelsolin **0.0072). Male (control vs PD male; *p<0.05) and aged patients had significantly higher levels of CFAH (CFAH, *p=0.043). Age vs. p-a-Syn (p=0.06; negative) and CNDP1 (p=0.0573; positive) showed active trends, suggesting a role in pathology. Besides, p-a-Syn showed a correlation with CFAH (p-a-Syn vs. CFAH *p=0.0167). Within the putamen, the neuropil of PD brains showed more CFAH-labelled profiles (PD vs. control, *p=0.0445); complemented by overexpression as well (PD vs. control **p=0.0043). In the caudate nucleus, the changes were limited to shrinkage of large profiles in the neuropil (PD vs. control **p=0.0079).
Conclusion: Higher serum-CFAH levels and more stained profiles validate its role in PD. The lower levels of p-a-Syn in PD serum match with other studies. Alterations in CNDP1, DKK3, and Gelsolin levels provide interesting insights of involvements of additional pathways PD pathology, that warrant detailed investigations.
To cite this abstract in AMA style:
P. Alladi, S. Choudhury, H. Jyothi, R. Bhavani, V. Holla, A. Mahadevan, N. Kamble, P. Pal, R. YADAV.. Serum based estimations of CFAH, Gelsolin, CNDP1 and DKK3 levels suggest involvement of multiple pathways in pathogenesis of Parkinson’s disease. [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/serum-based-estimations-of-cfah-gelsolin-cndp1-and-dkk3-levels-suggest-involvement-of-multiple-pathways-in-pathogenesis-of-parkinsons-disease/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/serum-based-estimations-of-cfah-gelsolin-cndp1-and-dkk3-levels-suggest-involvement-of-multiple-pathways-in-pathogenesis-of-parkinsons-disease/