Platelet-derived growth factor is increased with cognitive fluctuations and hallucinations in Lewy Body disease

Background: Cognitive fluctuations and hallucinations are common paroxysmal symptoms associated with Lewy body disease (LBD), which include Parkinson's disease, Parkinson's disease dementia and dementia with Lewy bodies. The exact pathophysiology underpinning cognitive fluctuations and visual hallucinations remains to be determined but evidence suggests that these transient symptoms could be linked to regional changes in cerebral blood flow, which in turn may occur due to dysfunction of the neurovascular unit. Objective: Platelet derived growth factor (PDGF) signalling plays a major role in the regulation of the neurovascular unit. Therefore, we aimed to determine if peripheral changes in PDGF signalling were associated with cognitive fluctuations and visual hallucinations in LBD. Methods: Two orthogonal approaches, employing antibody and aptamer-based assays respectively, were used to measure levels of PDGF and the PDGF receptor (PDGFRβ) in plasma samples from participants diagnosed with LBD, and then stratified into those experiencing cognitive fluctuations and visual hallucinations and those that did not. Results: The results using both measurement approaches demonstrated that plasma levels of PDGF family members were elevated in the LBD patients with cognitive fluctuations and visual hallucinations, compared to those without. Conclusions: The results suggest that PDGF signalling and potentially neurovascular uncoupling may play a role in these paroxysmal symptoms associated with LBD.