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Sphingolipids constitute a complex class of bioactive lipids with diverse structural and functional roles in neural tissue. Lipidomic techniques continue to provide evidence for their association in neurological diseases, including Parkinson’s disease (PD) and Lewy body disease (LBD). However, prior studies have primarily focused on biological tissues outside of the basal ganglia, despite the known relevancy of this brain region in motor and cognitive dysfunction associated with PD and LBD. Therefore electrospray ionization high resolution mass spectrometry was used to analyze levels of sphingolipid species, including ceramides (Cer), dihydroceramides (DHC), hydoxyceramides (OH-Cer), phytoceramides (Phyto-Cer), phosphoethanolamine ceramides (PE-Cer), sphingomyelins (SM), and sulfatides (Sulf) in the caudate, putamen and globus pallidus of PD (n = 7) and LBD (n = 14) human subjects and were compared to healthy controls (n = 9). The most dramatic alterations were seen in the putamen, with depletion of Cer and elevation of Sulf observed in both groups, with additional depletion of OH-Cer and elevation of DHC identified in LBD subjects. Diverging levels of DHC in the caudate suggest differing roles of this lipid in PD and LBD pathogenesis. These sphingolipid alterations in PD and LBD provide evidence for biochemical involvement of the neuronal cell death that characterize these conditions.

Human brain lipidomics have elucidated structural lipids and lipid signal transduction pathways in neurologic diseases. Such studies have traditionally sourced tissue exclusively from brain bank biorepositories, however, limited inventories signal that these facilities may not be able to keep pace with this growing research domain. Formalin fixed, whole body donors willed to academic institutions offer a potential supplemental tissue source, the lipid profiles of which have yet to be described. To determine the potential of these subjects in lipid analysis, the lipid levels of fresh and fixed frontal cortical gray matter of human donors were compared using high resolution electrospray ionization mass spectrometry. Results revealed commensurate levels of specific triacylglycerols, diacylglycerols, hexosyl ceramides, and hydroxy hexosyl ceramides. Baseline levels of these lipid families in human fixed tissue were identified via a broader survey study covering six brain regions: cerebellar gray matter, superior cerebellar peduncle, gray and subcortical white matter of the precentral gyrus, periventricular white matter, and internal capsule. Whole body donors may therefore serve as supplemental tissue sources for lipid analysis in a variety of clinical contexts, including Parkinson’s disease, Alzheimer’s disease, Lewy body dementia, multiple sclerosis, and Gaucher’s disease.

Background: Primary synovial chondromatosis (PSC) is a rare idiopathic pathology characterized by the formation of osseocartilaginous nodules within synovial joints, tendons, or bursae. The mineralization pattern of PSC nodules is poorly understood and has yet to be investigated using elemental analysis. Mapping this pattern could elucidate the progression of the disease.Materials and methods: PSC nodules discovered during dissection of a formalin fixed donor were analyzed. Scanning electron microscopy paired with energy dispersive X-ray spectroscopy (SEM-EDS) was used to quantify calcium and phosphorus levels to distinguish mineralized components from cartilage, indicated by increased carbon and oxygen concentrations.Results: Nine nodules with average dimensions 1.76cm x 1.25cm were identified in the semimembranosus bursa. SEM-EDS demonstrated increased calcium phosphate levels in nodular cores, while outer margins contained primarily carbon and oxygen. Quantification of these elements revealed nodular peripheries to contain 68.0% carbon, 30.2% oxygen, 0.8% calcium, and 1.0% phosphate, while cores were comprised of 38.1% carbon, 42.1% oxygen, 14.1% calcium, and 5.7% phosphate. Conclusions:Nodules were found to have mineralized cores embedded within a cartilaginous matrix. This pattern suggests disease progression is facilitated by endochondral ossification, opening the potential for new therapeutic techniques.

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