Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson's Disease?

Samar K Alselehdar,Suman Chowdhury,Roy N Alcalay,Robert Ledeen,Monami Chakraborty,Matthew Surface

doi:10.3390/ijms222111522

Abstract

The fact that Parkinson’s disease (PD) pathologies are well advanced in most PD patients by the time of clinical elucidation attests to the importance of early diagnosis. Our attempt to achieve this has capitalized on our previous finding that GM1 ganglioside is expressed at subnormal levels in virtually all tissues of sporadic PD (sPD) patients including blood cells. GM1 is present in most vertebrate cells, is especially abundant in neurons where it was shown essential for their effective functioning and long term viability. We have utilized peripheral blood mononuclear cells (PBMCs) which, despite their low GM1, we found to be significantly lower in sPD patients compared to age-matched healthy controls. To quantify GM1 (and GD1a) we used high performance thin-layer chromatography combined with cholera toxin B linked to horseradish peroxidase, followed by densitometric quantification. GM1 was also deficient in PBMCs from PD patients with mutations in the glucocerebrosidase gene (PD-GBA), apparently even lower than in sPD. Reasons are given why we believe these results obtained with patients manifesting fully developed PD will apply as well to PD patients in preclinical stages—a topic for future study. We also suggest that these findings point to a potential disease altering therapy for PD once the early diagnosis is established.

Highlights

Parkinson’s disease (PD) has been termed the fastest growing neurological disorder in the world [1], progressing in synchrony with the increasing age span of individuals worldwide
Lipid analysis was completed for a total of 23 sporadic PD (sPD) patients, 13 PD-GBA patients, and 21 agematched healthy controls, with males and females in each group
peripheral blood mononuclear cells (PBMCs) from sPD and PD-GBA patients and controls were analyzed in two separate cohorts

Summary

Introduction

Parkinson’s disease (PD) has been termed the fastest growing neurological disorder in the world [1], progressing in synchrony with the increasing age span of individuals worldwide. By the time of clear clinical diagnosis of PD half or more of the dopaminergic (DA) neurons of the nigrostriatal pathway have suffered viability decline or complete loss. Those DA neurons have received primary attention owing to their direct involvement in the movement disorders that constitute the clinical hallmarks of sporadic PD (sPD). Neurons throughout the body are affected before, during, and after the motor dysfunction sets in Treatment of these diverse populations with their associated symptoms would clearly be more effective if commenced early enough to prevent the extensive neuronal losses destined to occur, especially if accompanied by disease-altering therapy that would terminate progressive pathological changes

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