Gilbert Di Paolo

The paper identifies the CSF YWHAG:NPTX2 ratio as a biomarker for predicting clinical severity and phenoconversion in FTLD, showing strong correlation with disease progression and improved trial design potential.

This study shows lysosomal health influences myeloid cell states and immune responses, with Grn deficiency leading to lysosomal dysfunction and specific transcriptional changes in microglia.

This study shows that PGRN deficiency in microglia affects lipid metabolism, including reduced BMP and PE and increased GalCer, with age-dependent changes in Grn KO mice.

This study shows chronic NLRP3 inflammasome activation leads to neutrophil entry into the brain and interactions with microglia, contributing to CNS pathology.

This study investigates how TREM2 expression levels affect microglial function, metabolism, and response to TREM2 agonists in a mouse model of Alzheimer's disease.

This study shows the PD-risk GBA1 variant E326K reduces lysosomal GCase activity by disrupting LIMP2 interaction and causes lysosomal and mitochondrial dysfunction.

This study shows that LRRK2 kinase activity affects BMP and GSL levels in lysosomes, linking lysosomal dysfunction to Parkinson's disease through changes in GCase activity and BMP accumulation.

This study shows that GPR34 regulates microglia function and loss-of-function in TREM2 KO microglia rescues cholesterol metabolism, suggesting GPR34 as a therapeutic target for Alzheimer's disease.

This study identifies and characterizes lysosomal, glial, and neurodegenerative biomarkers in cerebrospinal fluid and plasma from FTD patients, revealing their correlation with disease severity and tissue changes.

This study shows that reduced progranulin leads to increased legumain activity, which promotes TDP-43 pathology in FTLD, suggesting legumain as a therapeutic target.

This study identifies genetic risk factors for early-onset Parkinson's Disease in a South Asian population, finding a genome-wide significant signal in the SNCA region and associations with BSN gene variants.

Peripheral AAV-mediated delivery of brain-penetrant PGRN rescues TDP-43 pathology, neurodegeneration and motor phenotypes in FTLD-GRN models.

This study shows that TREM2 deficiency reduces microglial hyperactivation in GRN-deficient models but does not rescue lysosomal dysfunction or neurodegeneration biomarkers.

This paper characterizes microglial metabolic changes in an APP knock-in mouse model of AD, finding lipid dysregulation and immunometabolic perturbations linked to fibrillar Aβ.