Fibrinogen and complement factor H: The two crucial markers of Parkinson's disease with cognitive impairment

Animal model-assisted validation is vital for biomarker studies. It provides better means for understanding disease pathogenesis and opens avenues for addressing therapeutics. Our earlier non-targeted label free proteomics-based biomarker study on CSF of Parkinsons disease (PD) patients with cognitive impairment (PDCI), revealed the presence of elevated levels of fibrinogen and complement factor H (CFAH) in PDCI-CSF. In the present study, we aimed to determine if these proteins harbor a pathogenic potential, when present above physiological levels. Native fibrinogen and recombinant CFAH were intraperitoneally injected in adult C57BL/6J mice and 48h later, motor and cognitive behavioral deficits as well as their neuroanatomical correlates were noted. The reduction in stride length in fibrinogen and CFAH injected mice indicate shuffling gait, often seen in PD patients. Motor deficit was complemented by the loss of dopaminergic (DA) neurons in SNpc, compensatory hypertrophy of the surviving neurons, and reduction in TH expression in striatum, thus reminiscing PD pathology. The low discrimination index in (novel object recognition) NOR test complemented by morphological alterations in Nissl-stained CA-1 and subiculum neurons in the fibrinogen-injected mice imply recognition memory deficits. Thus, our study provides objective evidence that fibrinogen and CFAH harbor the potential to induce motor deficits and cognitive impairments in mice, akin to the PDCI-associated neuro-pathological deficits, and thus are potential biomarkers.