Cerebrospinal fluid fatty acids in glucocerebrosidase‐associated Parkinson's disease

Abstract

Heterozygous mutations in the glucocerebrosidase gene lead to an increased risk for and to more severe alpha-synuclein-associated pathology in Parkinson's disease. As both glucocerebrosidase and alpha-synuclein interact with fatty acids, we hypothesized that cerebrospinal fluid fatty acid levels are altered in these Parkinson's disease patients. Cerebrospinal fluid levels of 13 fatty acids in 8 Parkinson's disease patients with a heterozygous glucocerebrosidase mutation were compared with those of 41 idiopathic Parkinson's disease patients and 30 controls using gas chromatography. Parkinson's disease patients with a heterozygous glucocerebrosidase mutation had lower levels of palmitoleic (P ≤ .007), oleic (P ≤ .016), linoleic (P ≤ .005), arachidonic (P ≤ .003), eicosapentaenoic (P ≤ .003) and decosahexaenoic (P ≤ .03) acids and lower levels of total fatty acids (P < .005) compared with both idiopathic Parkinson's disease patients and control subjects. These results suggest that abnormalities of fatty acid metabolism are specifically involved in the pathogenesis of Parkinson's disease associated with a heterozygous glucocerebrosidase mutation.