Leonard Petrucelli

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 that oral DBM treatment prevents cognitive decline in a C9ORF72 FTD mouse model without altering protein inclusions but corrects gene expression changes related to cytoskeleton, ALS, and metabolism.

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.

The paper decouples TDP-43 and Tau pathology in Alzheimer's disease by analyzing transcriptomic profiles and identifies subtype-specific transcriptional signatures.

This study identifies TDP-43-dependent cryptic splicing events in synaptic and membrane excitability genes and shows they drive neuronal dysfunction in ALS and FTD.

This study identifies epigenetic biomarkers in cell-free DNA for ALS diagnosis and progression prediction using methylation analysis.

The paper identifies TMEM106B fibril accumulation as a shared mechanism in neurodegeneration linked to genetic variants in TMEM106B and GRN.

The paper investigates factors determining TDP-43 seeding outcomes in FTLD-TDP, identifying TMEM106B fibrillar core and lysosomal escape as critical drivers.

The paper develops U7 snRNA therapeutics to correct TDP-43-dependent mis-splicing in ALS, restoring gene expression and neuronal function in human iPSC-derived neurons.

This study identifies ATP8A2 as a TDP-43 target whose loss leads to PS exposure and neuroinflammation, suggesting immune cell inhibition as a therapeutic strategy for ALS-FTD and CAMRQ4.

The paper identifies TDP-43-dependent molecular cascades in ALS/FTD by integrating multiomic data from iPSC-derived neurons and validates key genes through experimental assays.

This study identifies novel plasma proteins associated with KIF5A-linked SPG10 and ALS using targeted proteomics, revealing distinct proteomic signatures and potential biomarkers.

The paper identifies cryptic intronic C9orf72 transcripts as endogenous templates for RAN translation, leading to DPR production in ALS/FTD.

The paper shows that TDP-43 loss causes cryptic splicing events that are masked by nonsense-mediated decay, and inhibiting this decay reveals hundreds of novel splicing events.

This study identifies cryptic epitopes from de novo proteins caused by TDP-43 pathology as targets of CD8+ T cell activation in ALS and IBM.

This study identifies molecular subtypes based on cryptic exon burden in hippocampal tissue, revealing proteomic changes linked to TDP-43 pathology in LATE and Alzheimer's disease.

This study identifies genetic risk factors for FTLD-TDP subtypes using whole-genome sequencing and meta-analysis across multiple cohorts.

This study demonstrates that CRISPR-CasRx reduces C9orf72 repeat RNAs and DPRs in vitro and in vivo, suggesting its therapeutic potential for ALS/FTD.

ProtPipe is a data analysis pipeline for proteomics and peptidomics that automates processing, quality control, and downstream analysis of mass spectrometry data.

This paper develops and characterizes novel phospho-ubiquitin antibodies to detect low levels of p-S65-Ub, a marker of mitochondrial damage, in cells and tissues.

The paper shows that ribosomal quality control factors reduce toxic repeat-associated non-AUG translation from GC-rich repeats by preventing ribosomal stalling.

The paper shows that loss of TDP-43 function leads to the expression of de novo proteins from mis-spliced mRNA transcripts in ALS/FTD.

This study shows that TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes affecting disease-relevant genes.

The paper identifies an AluYb8 retrotransposon in a TMEM106B risk haplotype associated with neurodegeneration, linking it to age-related dysregulation and population-specific disease risk.

This study identifies GSDME as a mediator of mitochondrial damage and axon loss in neurodegenerative diseases, showing its role in ALS and FTD models.

This study shows FUS suppresses RAN translation by modulating G-quadruplex structure of GGGGCC repeat RNA, reducing neurodegeneration in C9-ALS/FTD model flies.

This study evaluates human-derived anti-poly-GA antibodies in cellular and animal models of C9ORF72 disease, showing mixed effects on poly-GA levels and disease progression.

This study removes a hexanucleotide repeat expansion in C9ORF72 using CRISPR/Cas9 in cell and animal models, reducing disease hallmarks.

This study shows that TDP-43 represses a cryptic exon in UNC13A, and genetic variants associated with FTD/ALS increase cryptic exon inclusion when TDP-43 is dysfunctional.