Biology subjects

Di Biase, E.

Publications and source records attributed to Di Biase, E..

2 recordsLinked to original sources

bioRxiv2026

GPNMB and glycosphingolipid measurements in cerebrospinal fluid and plasma from Parkinson's disease patients in the BioFind cohort

BackgroundParkinsons disease (PD) is a prevalent neurodegenerative disorder characterized by progressive motor dysfunction and broad cellular impairment, including significant disruptions in lysosomal function, lipid metabolism, and intracellular trafficking. Glycosphingolipids (GSLs), critical for various cellular processes, depend on effective lysosomal degradation. Aberrant GSL metabolism has been linked to PD pathology, and glycoprotein non-metastatic melanoma protein B (GPNMB) has emerged as a biomarker associated with lysosomal dysfunction and lipid imbalance in PD ObjectivesTo assess the relationship between GPNMB and GSL levels in cerebrospinal fluid (CSF) and plasma from PD patients and controls within the BioFIND cohort. We also investigated potential sex differences and associations with PD-related biomarkers such as -synuclein MethodsGSL species and GPNMB protein levels were quantified using high-performance liquid chromatography (HPLC) and ELISA assays, respectively, in matched CSF and plasma samples from PD patients and controls ResultsLevels of the paraglobosides GSL species, alpha-2,3SpG and pGb were significantly elevated in the plasma of PD patients compared to healthy controls, while levels of the ganglioside GD1a and the lacto-series GSL, Leb combined (GD1a + Leb), were significantly reduced in PD. GPNMB levels positively correlated with several GSL species in both plasma and CSF. Plasma GSLs and GPNMB concentrations were significantly higher in females compared to males, independent of PD diagnosis. CSF GPNMB correlated positively with age and -synuclein concentrations InterpretationOur findings confirm that GSL metabolism is altered in PD. They also highlight significant sex-based biochemical variations in GSL and GPNMB levels, emphasizing the need for sex-specific analyses in PD biomarker research. The relationship between GSLs and GPNMB supports their potential as interconnected biomarkers of lipid pathology in PD.

neuroscience↗

bioRxiv2025

APOE3 astrocytes can rescue lipid abnormalities and dystrophic neurites of APOE4 human neurons

Lipid abnormalities are emerging as key pathogenic mechanisms in neurodegenerative diseases such as Alzheimers, Parkinsons and Lewy body dementia. Astrocytes in the brain provide APOE proteins and influence neuronal metabolism and health. Using live cell imaging and objective neurite imaging techniques, we show that following induction of cellular lipid (cholesterol and triglycerides) load by inhibiting the lysosomal cholesterol transport protein NPC1 in human neuron-astrocyte co-cultures, that human astrocytes CRISPR edited to be either APOE3 or 4 variants have different effects on rescuing dystrophic neurites, where axons and dendrites of nerve cells become disfigured. APOE3, but not APOE4 or APOEKO, astrocytes prevented cholesterol and lipid induced neurite damage in APOE4 neurons. In the media of APOE3 co-cultured astrocytes with neurons the HDL-like particles were larger and presumably more lipidated than equivalent APOE4 co-cultures. This discovery highlights that living APOE3 astrocytes control key biological mechanisms by physiologically enhancing lipid cellular homeostasis, that can rescue lipid-induced neurite structural abnormalities relevant to Alzheimers disease and neurodegenerative diseases. Significance statementNeurodegenerative diseases like Alzheimers (AD) are often defined by abnormal protein aggregates, but growing evidence points to lipid dysfunction as a key driver, especially in APOE4 carriers, the strongest genetic risk factor for AD. We developed a live cell imaging based human cell culture model using isogenic iPSC-derived neurons and astrocytes (APOE3, APOE4, or APOE knockout) to study this. By blocking cholesterol export via NPC1 inhibition, we mimicked lysosomal lipid stress and found that APOE3 astrocytes uniquely protected APOE4 neurons from forming abnormal neurite swellings. These APOE3 astrocytes produced larger HDL-like particles than APOE4 that supported neuronal lipid balance. Our results show that APOE3 astrocytes can rescue APOE4-related cellular dysfunction, offering a potential path for therapy and biomarker discovery.

neuroscience↗