Abstract
Parkinson's disease (PD) is the second commonest neurodegenerative disorder in the world with a rising prevalence. The pathophysiology is multifactorial but aggregation of misfolded alpha-synuclein is considered to be a key underpinning mechanism. Amyloid-beta (Abeta) and tau deposition are also comorbid associations and especially Abeta deposition is associated with cognitive decline in PD. Some existing evidence suggests that low cerebrospinal fluid (CSF) Abeta42 is predictive of future cognitive impairment in PD. Recent studies also show that CSF Abeta is associated with the postural instability and gait difficulties (PIGD) or the newly proposed cholinergic subtype of PD, a possible risk factor for cognitive decline in PD. The glial-lymphatic system, responsible for convective solute clearance driven by active fluid transport through aquaporin-4 water channels, may be implicated in brain amyloid deposition. A better understanding of the role of this system and more specifically the role of Abeta in PD symptomatology, could introduce new treatment and repurposing drug-based strategies. For instance, apomorphine infusion has been shown to promote the degradation of Abeta in rodent models. This is further supported in a post-mortem study in PD patients although clinical implications are unclear. In this review, we address the clinical implication of cerebral Abeta deposition in PD and elaborate on its metabolism, its role in cognition and motor function/gait, and finally assess the potential effect of apomorphine on Abeta deposition in PD.
