Gaucher cells are not associated with α-synuclein neuropathology in infants

Abstract

A link between Gaucher disease (GD) and Parkinson disease (PD) has been suggested by many studies. Lewy-body-like α-synuclein inclusions have been shown in older GD patients who developed Parkinsonism. It has been proposed that decreased levels of glucocerebrosidase mediate impaired α-synuclein degradation and hence its accumulation. Nevertheless, this phenomenon is less investigated in the infantile form of GD. The aim of the study was to evaluate α-synuclein and τ-pathology in the brain and non-neural tissues (liver, spleen, pancreas, myocardial muscle, and lung) of 5 infants (age range from 1 month to 4 years) with GD. Our immunohistochemical study did not provide evidence that pathological α-synuclein or τ-accumulates early in tissues where Gaucher cells are already prominently present. Although recent finding of altered plasma α-synuclein levels in infantile GD patients suggest an early imbalance of α-synuclein homeostasis, our findings indicate that this does not inevitably coincide with α-synuclein pathology in the brain. Understanding this temporal variance of plasma levels and brain accumulation of α-synuclein might also be important when interpreting blood-based α-synuclein assays for the diagnosis of PD.