Postmortem Fatty Acid Abnormalities in the Cerebellum of Patients with Essential Tremor

• Published in: Cerebellum (London, England)
• Main Authors: Simard, Mélissa, Mélançon, Koralie, Berthiaume, Line, Tremblay, Cyntia, Pshevorskiy, Laura, Julien, Pierre, Rajput, Ali H, Rajput, Alex, Calon, Frédéric
• Format: Journal Article
• Language: English
• Published: United States 31.08.2024
• Subjects: Essential tremor (ET); Omega-3 polyunsaturated fatty acids (ω-3 PUFA); Fatty acids; Glycerophospholipids
• ISSN: 1473-4230; 1473-4230
• DOI: 10.1007/s12311-024-01736-4

Fatty acids play many critical roles in brain function but have not been investigated in essential tremor (ET), a frequent movement disorder suspected to involve cerebellar dysfunction. Here, we report a postmortem comparative analysis of fatty acid profiles by gas chromatography in the cerebellar cortex from ET patients (n = 15), Parkinson's disease (PD) patients (n = 15) and Controls (n = 17). Phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI)/ phosphatidylserine (PS) were separated by thin-layer chromatography and analyzed separately. First, the total amounts of fatty acids retrieved from the cerebellar cortex were lower in ET patients compared with PD patients, including monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). The diagnosis of ET was associated with lower cerebellar levels of saturated fatty acids (SFA) and PUFA (DHA and ARA) in the PE fraction specifically, but with a higher relative content of dihomo-γ-linolenic acid (DGLA; 20:3 ω-6) in the PC fraction. In contrast, a diagnosis of PD was associated with higher absolute concentrations of SFA, MUFA and ω-6 PUFA in the PI + PS fractions. However, relative PI + PS contents of ω-6 PUFA were lower in both PD and ET patients. Finally, linear regression analyses showed that the ω-3:ω-6 PUFA ratio was positively associated with age of death, but inversely associated with insoluble α-synuclein. Although it remains unclear how these FA changes in the cerebellum are implicated in ET or PD pathophysiology, they may be related to an ongoing neurodegenerative process or to dietary intake differences. The present findings provide a window of opportunity for lipid-based therapeutic nutritional intervention.