Objective: To examine the levels of putative biomarkers FIB, CFAH, gelsolin (GSN), α-syn and phosphorylated-α-syn in PD serum. To localize and quantify FIB and CFAH in autopsied brains of PD patients.

Background: Fibrinogen (FIB), a plasma coagulation factor that represent BBB breach, complement factor-H (CFAH) and gelsolin were elevated in the CSF of Parkinson’s disease (PD) patients and in PD patients with cognitive impairment (PDCI). α-Synuclein (α-Syn) a reliable marker of PD, was unaltered in an Indian cohort.

Method: Serum being a better biofluid in terms of ease of collection, was used to estimate protein levels. Samples collected from age matched non-neurological controls (50-65 yr, n=42); PD patients (48-76 yr; n=60) and PDCI (50-77 yr, n=20) were subjected to ELISA-based quantification using commercially available kits for Fibrinogen and CFAH, Gelsolin, α-syn and p-α-Syn. The data was analyzed using Kruskal Wallis or Mann Whitney test. We also examined 5μ formalin-fixed paraffin-embedded striatal sections from normal aged subjects who died in road traffic accidents and PD patients. Immunofluorescence-based staining was performed for FIB and CFAH and quantification was performed using confocal microscopy.

Results: Fibrinogen and CFAH were elevated in the serum of PD and PDCI patients. The PD and PDCI patients show significantly higher levels of fibrinogen (vs Control, ****p<0.0001; vs Control, **p<0.01), CFAH (Control vs PD; ***p<0.001; Control vs PDCI; *p<0.05) and GSN compared to the controls. A-Syn showed no intergroup differences, whereas, p-α-synuclein was significantly lower in PD. FIB expression was upregulated in the striatal blood vessels and putamenal neuropil of PD patients compared to the young (p=.030). In PD, the lumen of blood vessels  near the ventricles showed intense presence as well (vascular vs perivascular, p=0.045; vascular vs peri-lumen, p=0.020). A significant increase in the no. of FIB + profiles (p=0.048) in ventricular peri-lumen was noted too. CFAH expression was upregulated in the putamen near the blood vessels (p=*0.0498) and in neuropil (p=**0.0079) of PD patients. It was highest in the blood vessel lumen near the ventricles (**p=0.0065). An increase in the no. of CFAH + profiles (p=0.048) was also noted around the ventricles-associated blood vessels(**p=0.0022).

Conclusion:

FIB, CFAH and gelsolin are implied in PD pathology and along with α-syn levels, may be useful in understanding pathogenesis.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/fibrinogen-and-cfah-as-putative-biomarkers-for-parkinsons-disease/