Neil A. Shneider

Exploring transcriptomic and genomic latent variable correction approaches in differential expression analysis.

This paper evaluates combining expression-based surrogate variables and genotype-based principal components in differential expression analysis, finding the combined approach improves replicability and biological recall in ALS datasets.

Clonal CD8 T cells in the leptomeninges are locally controlled and influence microglia in human neurodegeneration

The paper identifies clonal CD8 T cell activation in human meninges and their regulatory role in controlling neuroinflammation through interactions with natural killer cells.

Amygdala TDP-43 pathology is associated with behavioural dysfunction and ferritin accumulation in amyotrophic lateral sclerosis.

The paper shows that amygdala TDP-43 pathology correlates with behavioural dysfunction and ferritin accumulation in sporadic ALS.

A mouse model of CHCHD10 p.R15L familial ALS presents mild, age-related motor neuron degeneration without protein instability or mitochondrial dysfunction

Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells

This study shows that loss of nuclear TDP-43 in microglia-like cells disrupts lipid metabolism, leading to increased lipid droplets, phagocytosis, and inflammation, which can be mitigated by DGAT inhibitors.

Amyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration.

The paper identifies amyloid fibril structures of CHCHD10 and links them to neurodegeneration, showing sequence differences between CHCHD10 and CHCHD2 allow co-aggregation.

Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord

The paper identifies microglia subsets in ALS brain and spinal cord, finding an undifferentiated phenotype and enrichment of interferon response microglia in aggressive cases.

Computationally Designed RNA Aptamers Enable Selective Detection of FUS Pathology in ALS

This study uses RNA aptamers to detect pathological FUS in ALS, showing improved specificity and sensitivity compared to antibodies.

A proteogenomic tool uncovers protein markers for human microglial states

The paper introduces a proteomic tool to identify protein markers for human microglial states and validates their utility in purification and differentiation.

A factor-based analysis of individual human microglia uncovers regulators of an Alzheimer-related transcriptional signature

The paper uses single-cell data to identify factors regulating an Alzheimer's disease-related microglial signature and proposes a new analytic framework for microglial classification.

RNA aptamer reveals nuclear TDP-43 pathology is an early aggregation event that coincides with STMN-2 cryptic splicing and precedes clinical manifestation in ALS

This study uses an RNA aptamer to detect TDP-43 aggregation and shows that nuclear TDP-43 pathology and STMN-2 cryptic splicing occur before clinical symptoms in ALS.

A scalable screening platform for phenotypic subtyping of ALS patient-derived fibroblasts

The paper develops a scalable platform combining microscopy and machine learning to subtype ALS patient fibroblasts, identifying a FUS-ALS phenotypic score that correlates with age and treatment response.

A multiplex platform to identify mechanisms and modulators of proteotoxicity in neurodegeneration

The paper develops a multiplex reverse genetics platform to identify genetic modifiers of protein misfolding in neurodegenerative diseases and identifies DNAJB6 as a modifier of toxicity and solubility of ALS/FTD-linked RNA-binding proteins.

A cross-disease human microglial framework identifies disease-enriched subsets and tool compounds for microglial polarization.

This study identifies disease-enriched microglial subsets and validates compounds that modulate their states using single-cell RNA sequencing and in vitro experiments.

Cell environment shapes TDP-43 function: implications in neuronal and muscle disease

The paper compares TDP-43's transcriptional and splicing effects in muscle and neuronal cells, showing tissue-specific roles in disease.

Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia

The paper uses unsupervised machine learning to identify three molecular subtypes in ALS cortex samples, associated with oxidative stress, retrotransposon activation, and glial activation.

Regional collapsing of rare variation implicates specific genic regions in ALS

The paper applies two novel collapsing methods to ALS sequencing data to identify risk regions in known ALS genes and candidate genes.