Objective: To determine the pathogenic potential of fibrinogen and complement factor H (CFAH) in causing Parkinson’s disease (PD) with cognitive impairment (PDCI)-like symptoms using C57BL/6J mice.
Background: According to our earlier unbiased label free proteomics-based study, fibrinogen and CFAH were the maximally upregulated proteins in the CSF of PDCI patients. In order to consider these proteins as biomarkers of PDCI it is imperative to investigate if they have a pathogenic potential, using an animal model.
Method: Following i.p. injection of native fibrinogen and recombinant CFAH proteins in C57BL/6J mice, we performed behavioral tests such as gait analysis and pole test to assess motor behavior followed by NOR test to determine the effects on cognition. The neuropathological correlates underlying the motor deficiencies were assessed by counting the dopaminergic (DA) neurons of the SNpc using unbiased stereology, tyrosine hydroxylase (TH) expression in the SNpc and striatal dopamine level by densitometry. The cognitive correlates were assessed by cytomorphological study of the nucleus and cytoplasm of the hippocampal subfields CA1 and subiculum using Leica LAS-X software.
Results: On the pole, the fibrinogen injected mice took longer time to descend suggesting bradykinesia. Stride length which is a spatial gait parameter was reduced in fibrinogen and CFAH injected mice indicating shuffling of gait. The working memory was affected in fibrinogen-group as evinced by the low discrimination index in the NOR test. Loss of dopaminergic neurons in the SNpc and lower TH expression in the SNpc and striatum were observed in the fibrinogen-mice. Surviving nigral DA neurons showed hypertrophy as a compensation to the loss of DA neurons in both the groups. Additionally, hypertrophic neurons were observed in CA1 and subiculum hinting at cognitive decline.
Conclusion: Fibrinogen and CFAH are the two putative markers of PDCI as they induced motor and cognitive impairments akin to the neuropathological deficits associated with PDCI.
To cite this abstract in AMA style:
A. Naskar, S. M, S. Sengupta, P. Pal, P. Alladi. Fibrinogen and CFAH: The two putative markers of Parkinson’s disease with cognitive impairment [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/fibrinogen-and-cfah-the-two-putative-markers-of-parkinsons-disease-with-cognitive-impairment/. Accessed June 15, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/fibrinogen-and-cfah-the-two-putative-markers-of-parkinsons-disease-with-cognitive-impairment/