Amyloid-β and Parkinson's disease

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 (A beta) and tau deposition are also comorbid associations and especially A beta deposition is associated with cognitive decline in PD. Some existing evidence suggests that low cerebrospinal fluid (CSF) A beta(42) is predictive of future cognitive impairment in PD. Recent studies also show that CSF A beta 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 A beta in PD symptomatology, could introduce new treatment and repurposing drug-based strategies. For instance, apomorphine infusion has been shown to promote the degradation of A beta 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 A beta 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 A beta deposition in PD.