Explanipedia

Gene expression signatures from whole blood predict amyotrophic lateral sclerosis case status and survival Open

Yue Zhao, Masha G. Savelieff, Xiayan Li, Kai Guo, Kai Wang , et al. · 2025

TDP-43 loss induces cryptic polyadenylation in ALS/FTD Open

Sam Bryce-Smith, Anna‐Leigh Brown, Max Z. Y. J. Chien, Dario Dattilo, Puja R. Mehta , et al. · 2025

Nuclear depletion and cytoplasmic aggregation of the RNA-binding protein TDP-43 are cellular hallmarks of amyotrophic lateral sclerosis (ALS). TDP-43 nuclear loss causes de-repression of cryptic exons, yet cryptic alternative polyadenylati…

Integrating a motor domain enhances disease severity scales in an FTD‐ALS spectrum cohort Open

Allison Snyder, Kiran Samra, Tianxia Wu, Lucy L. Russell, Jennifer Farren , et al. · 2025

INTRODUCTION The Genetic Frontotemporal Initiative (GENFI) and Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)‐Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Longitudinal Fronto…

A plasma proteomics-based candidate biomarker panel predictive of amyotrophic lateral sclerosis Open

Ruth Chia, Ruin Moaddel, Justin Kwan, Memoona Rasheed, Paola Ruffo , et al. · 2025

Identifying a reliable biomarker for amyotrophic lateral sclerosis (ALS) is crucial for clinical practice. Here, in this cross-sectional study, we used the Olink Explore 3072 platform to investigate plasma proteomics as a biomarker tool fo…

FUS Mislocalization Rewires a Cortical Gene Network to Drive Cognitive and Behavioral Impairment in ALS Open

Raphaelle Cassel, Félicie Lorenc, Aurélie Bombardier, Claudia De Tapia, Stéphane Dieterle , et al. · 2025

Summary Cognitive and behavioral impairment affects up to half of individuals with amyotrophic lateral sclerosis (ALS), but their molecular origin remains unresolved. Here, we identify mislocalization of the RNA-binding protein FUS in cort…

KIF5Ap.Pro986Leu Risk Variant and Accelerated Progression of Amyotrophic Lateral Sclerosis Open

Arianna Manini, Rosario Vasta, Alberto Brusati, Francesco Scheveger, Silvia Peverelli , et al. · 2025

This study explored the impact of KIF5A rs113247976 (p.Pro986Leu), a risk allele for amyotrophic lateral sclerosis (ALS), on phenotypic variability in two Italian ALS cohorts (discovery, n = 865; replication, n = 1174). The minor allele (T…

Unveiling the regulatory potential of the non-coding genome: Insights from the human genome project to precision medicine Open

Paola Ruffo, Bryan J. Traynor, F. L. Conforti · 2025

The Human Genome Project marked a milestone in scientific exploration, unraveling the genetic blueprint of humanity. However, expectations of direct gene-disease associations gave way to realizing the complexity of genetic interactions, es…

CREB3 gain of function variants protect against ALS Open

Salim Megat, Christine Marques, Marina Hernán-Godoy, Chantal Sellier, Geoffrey Stuart‐Lopez , et al. · 2025

The interneuron hypothesis of amyotrophic lateral sclerosis Open

Bryan J. Traynor · 2025

Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects Open

Paola Ruffo, Bryan J. Traynor, F. L. Conforti · 2025

Characterization of DNA methylation in PBMCs and donor-matched iPSCs shows methylation is reset during stem cell reprogramming Open

Xylena Reed, Cory A. Weller, Sara Sáez-Atiénzar, Alexandra Beilina, Sultana Solaiman , et al. · 2024

Summary DNA methylation is an important epigenetic mechanism that helps define and maintain cellular functions. It is influenced by many factors, including environmental exposures, genotype, cell type, sex, and aging. Since age is the prim…

CREB3gain of function variants protect against ALS Open

Salim Megat, Christine Marques, Marina Hernan Godoy, Chantal Sellier, Geoffrey Stuart‐Lopez , et al. · 2024

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly evolving neurodegenerative disease that arises from the loss of glutamatergic corticospinal neurons (CSN) and cholinergic motoneurons (MN). The disease is mostly sporadic, but gene…

Therapeutic development approaches to treat haploinsufficiency diseases: restoring protein levels Open

Elena F Evans, Zeenat A. Shyr, Bryan J. Traynor, Wei Zheng · 2024

Rare diseases affect one in ten people but only a small fraction of these diseases have an FDA-approved treatment. Haploinsufficiency, caused by a dominant loss-of-function mutation, is a unique rare disease group because patients have one…

Epigenetic age acceleration is associated with occupational exposures, sex, and survival in amyotrophic lateral sclerosis Open

Yue Zhao, Xiayan Li, Kai Wang, Gayatri Iyer, Stacey A. Sakowski , et al. · 2024

NIH, CDC/National ALS Registry, ALS Association, Dr. Randall Whitcomb Fund for ALS Genetics, Peter Clark Fund for ALS Research, Sinai Medical Staff Foundation, Scott L. Pranger ALS Clinic Fund, NeuroNetwork Therapeutic Discovery Fund, Neur…

NeuroBooster Array: A Genome‐Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations Open

Sara Bandrés‐Ciga, Faraz Faghri, Elisa Majounie, Mathew J. Koretsky, Jeffrey Kim , et al. · 2024

Background Commercial genome‐wide genotyping arrays have historically neglected coverage of genetic variation across populations. Objective We aimed to create a multi‐ancestry genome‐wide array that would include a wide range of neuro‐spec…

IntermediateHTTCAG repeats worsen disease severity in amyotrophic lateral sclerosis Open

Maurizio Grassano, Antonio Canosa, Sandra D'Alfonso, Lucia Corrado, Giorgia Brodini , et al. · 2024

Genome-Wide and Transcriptome-Wide Association Studies on Northern New England and Ohio Amyotrophic Lateral Sclerosis Cohorts Open

Siting Li, Jiang Gui, Michael N. Passarelli, Angeline S. Andrew, Kathleen M. Sullivan , et al. · 2024

Our results support the need for future evaluation to clarify the role of these potential genetic risk factors for ALS and to understand genetic susceptibility to environmental risk factors.

Computing linkage disequilibrium aware genome embeddings using autoencoders Open

Gizem Taş, Timo Westerdijk, Eric Postma, Wouter van Rheenen, Mark K. Bakker , et al. · 2024

Motivation The completion of the genome has paved the way for genome-wide association studies (GWAS), which explained certain proportions of heritability. GWAS are not optimally suited to detect non-linear effects in disease risk, possibly…

Author Correction: A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS–FTD Open

Katherine E. Irwin, Pei Jasin, Kerstin E. Braunstein, Irika R. Sinha, Mark A. Garret , et al. · 2024

Genetic analysis of the X chromosome in people with Lewy body dementia nominates new risk loci Open

Ece Bayram, Paolo Reho, Irene Litvan, Jinhui Ding, J. Raphael Gibbs , et al. · 2024

Sex influences the prevalence and symptoms of Lewy body dementia (LBD). However, genome-wide association studies typically focus on autosomal variants and exclude sex-specific risk factors. We addressed this gap by performing an X chromoso…

A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS–FTD Open

Katherine E. Irwin, Pei Jasin, Kerstin E. Braunstein, Irika R. Sinha, Mark A. Garret , et al. · 2024

Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies Open

Paolo Reho, Sara Sáez-Atiénzar, Paola Ruffo, Sultana Solaiman, Zalak Shah , et al. · 2024

Investigation of the genetic aetiology of Lewy body diseases with and without dementia Open

Lesley Wu, Raquel Real, Alejandro Martínez-Carrasco, Ruth Chia, Michael Lawton , et al. · 2024

Up to 80% of Parkinson's disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson’s disease dementia, but cognitive impai…

Genomic analysis identifies risk factors in restless legs syndrome Open

Fulya Akçimen, Ruth Chia, Sara Sáez-Atiénzar, Paola Ruffo, Memoona Rasheed , et al. · 2023

Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletel…

Association of cardiovascular disease management drugs with Lewy body dementia: a case–control study Open

Sonja W. Scholz, Brian Moroz, Sara Sáez-Atiénzar, Ruth Chia, Elizabeth K. Cahoon , et al. · 2023

Lewy body dementia is the second most common neurodegenerative dementia after Alzheimer’s disease. Disease-modifying therapies for this disabling neuropsychiatric condition are critically needed. To identify drugs associated with the risk …

A novel fluid biomarker for TDP‐43 loss of function Open

Katherine E. Irwin, Pei Jasin, Kerstin E. Braunstein, Irika R. Sinha, Kyra D. Bowden , et al. · 2023

Background TDP‐43 nuclear clearance and cytoplasmic aggregation occur in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis‐frontotemporal dementia (ALS‐FTD), Alzheimer’s disease (AD), and limbic‐predominant age‐r…

Structural variants in Lewy body dementia and frontotemporal dementia spectrum Open

Karri Kaivola, Ruth Chia, Jinhui Ding, Memoona Rasheed, Masashi Fujita , et al. · 2023

Background Structural variants range from simple loss or gain of genetic material to complex events that restructure entire chromosomes. This heterogeneity coupled with variant size greater than sequencing read‐length makes structural vari…

NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations Open

Sara Bandrés‐Ciga, Faraz Faghri, Elisa Majounie, Mathew J. Koretsky, Jeffrey Kim , et al. · 2023

Genome-wide genotyping platforms have the capacity to capture genetic variation across different populations, but there have been disparities in the representation of population-dependent genetic diversity. The motivation for pursuing this…

Investigation of the genetic aetiology of Lewy body diseases with and without dementia Open

Lesley Wu, Raquel Real, Alejandro Martínez-Carrasco, Ruth Chia, Michael Lawton , et al. · 2023

Up to 80% of Parkinson’s disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson’s disease dementia, but cognitive impai…

Roadmap for C9ORF72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis: Report on the C9ORF72 FTD/ALS Summit Open

Rita Sattler, Bryan J. Traynor, Janice Robertson, Ludo Van Den Bosch, Sami J. Barmada , et al. · 2023

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