Application of Sebum Lipidomics to Biomarkers Discovery in Neurodegenerative Diseases

Abstract

Lipidomics is strategic in the discovery of biomarkers of neurodegenerative diseases (NDDs). The skin surface lipidome bears the potential to provide biomarker candidates in the detection of pathological processes occurring in distal organs. We investigated the sebum composition to search diagnostic and, possibly, prognostic, biomarkers of Alzheimer’s disease (AD) and Parkinson’s disease (PD). The observational study included 64 subjects: 20 characterized as “probable AD with documented decline”, 20 as “clinically established PD”, and 24 healthy subjects (HS) of comparable age. The analysis of sebum by GCMS and TLC retrieved the amounts (µg) of 41 free fatty acids (FFAs), 7 fatty alcohols (FOHs), vitamin E, cholesterol, squalene, and total triglycerides (TGs) and wax esters (WEs). Distributions of sebum lipids in NDDs and healthy conditions were investigated with multivariate ANOVA-simultaneous component analysis (ASCA). The deranged sebum composition associated with the PD group showed incretion of most composing lipids compared to HS, whereas only two lipid species (vitamin E and FOH14:0) were discriminant of AD samples and presented lower levels than HS sebum. Thus, sebum lipid biosynthetic pathways are differently affected in PD and AD. The characteristic sebum bio-signatures detected support the value of sebum lipidomics in the biomarkers search in NDDs.

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

“…More recently, as changes in the circulating lipids seem to mirror the dysregulation of their profile in the brain, blood has become a viable alternative to invasive CSF sampling [ 299 , 300 , 301 ]. At the same time, the emergence of cutting-edge techniques, such as peripheral lipidomics, triple quadrupole mass spectrometry, and isobaric tagging methods, have allowed the establishment of lipid signatures potentially associated with AD, even at the prodromal and preclinical stages [ 302 , 303 , 304 ]. Lipid peroxidation, caused by oxidative stress, is one of the most-studied markers of disease, and various molecules have been proposed as potential circulating biomarkers (See Section 3.5 Oxidative Stress ) [ 166 , 167 , 182 , 305 , 306 , 307 ].…”

“…Yet, some particularly advanced and cutting-edge techniques, such as peripheral lipidomics, triple quadrupole mass spectrometry, and isobaric tagging methods, are particularly burdensome for clinical routine analysis, and here were described for completeness, whereas others are very rarely applied [ 302 , 303 , 304 ].…”

Sensitivity of Sniffer Dogs for a Diagnosis of Parkinson's Disease: A Diagnostic Accuracy Study

“…22 Our observation is in line with previous studies that compared medicated and drug-naïve patients with PD, demonstrating that PD medication does not influence production of the compounds responsible for the PD smell. 10,21 Studies show that compounds in the sebum of patients with PD are different from that of non-PD subjects, 10,21,23,24 and the dogs may have taken this advantage to distinguish them.…”

Current insights into skin lipids and their roles in cutaneous health and disease

“…In this context, epidermal ceramides and sebum lipids have been examined as potential biomarkers of neurodegenerative disease [66 ▪ ,67], and a recent study on the sebum metabolome suggested lipid dysregulation in Parkinson's disease [68 ▪▪ ]. Interestingly, sphingoid base profiles in infant skin can predict the development of atopic dermatitis [69 ▪ ].…”