Fibrinogen and Complement Factor H Induce Parkinsonian and Cognitive Impairment-Like Features in Mice

Cognitive impairment is one of the non-motor symptoms of Parkinson's disease (PD), which may precede motor impairment. Biomarker(s) can help detect the cognitive dysfunction, much earlier in the disease and may differentiate PD patients with and without cognitive impairments. Animal model-based biomarker validation studies can provide better insights into pathogenesis and open up avenues for addressing therapeutics; however, such studies using non-genetic modalities, are few. Our earlier non-targeted label-free proteomics-assisted biomarker study on CSF of PD patients with cognitive impairment (PDCI), revealed the presence of elevated levels of fibrinogen and complement factor H (CFAH) in PDCI-CSF. We now intend 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 48 h later the motor and cognitive behavior alongside neuroanatomical correlates were studied. The motor and cognitive deficits were complemented by degenerative changes in the SNpc, striatum, CA1 and subiculum in the injected mice. The altered gut microarchitecture suggests the possibility of other non-motor symptoms. Here, we show that fibrinogen and CFAH can potentially induce motor, and non-motor deficits in mice, akin to the PDCI-associated neuropathological deficits, and thus are potential biomarkers.