Rosa Rademakers

Targeted single-nucleus sequencing of 39,800 neurons reveals extensive low-frequency somatic variants

The paper analyzes somatic mutations in neurons from FTLD-TDP type C patients and controls, finding extensive low-frequency variants in TARDBP and other genes.

Cerebrospinal fluid YWHAG:NPTX2 ratio predicts clinical severity and future phenoconversion in frontotemporal lobar degeneration

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.

inquiSTR: a toolkit for accurate and efficient population-scale tandem repeat genotyping and analysis

inqiSTR is a toolkit for efficient and accurate tandem repeat genotyping from long-read sequencing data, enabling population-scale analysis and downstream applications.

Distinct TAF15 amyloid filament folds define multiple subtypes of FTLD-TAF15

This study identifies distinct TAF15 amyloid filament structures in different FTLD-FET subtypes, leading to the renaming of the disease group as FTLD-TAF15.

Identification of common variants influencing risk of the three-repeat tauopathy Pick's disease: a genome wide association study.

This study conducts a GWAS on Pick's disease and identifies two SNPs associated with risk, though not at genome-wide significance, suggesting potential genetic factors beyond MAPT mutations.

Expanding the spectrum of annexin A11 proteinopathy in frontotemporal lobar degeneration and motor neuron disease

The paper characterizes ANXA11 proteinopathy in FTLD-PLS and MND-TDP cases, showing it is common in FTLD-PLS but not linked to pathogenic ANXA11 variants or TDP type C.

Differential neuronal vulnerability to C9orf72 repeat expansion driven by Xbp1 transcription signature

The paper identifies neuronal vulnerability to C9orf72 repeat expansion by analyzing transcriptional states in a Drosophila model, finding that Xbp1 expression correlates with resistance to toxicity.

Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia

This study examines sex differences in clinical progression of autosomal dominant frontotemporal dementia, finding females show more rapid declines in symptomatic stages and less sensitive NfL prognostic value.

Methylmap: visualization of modified nucleotides for large cohort sizes

Methylmap visualizes modified nucleotide frequencies across positions for large sample cohorts using standardized BAM/CRAM files.

Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes

This study identifies six genetic loci associated with progressive supranuclear palsy, including a novel locus, and links them to oligodendrocytic dysfunction and C4A expression.

Whole-Genome Sequencing Analysis Reveals New Susceptibility Loci and Structural Variants Associated with Progressive Supranuclear Palsy

This study uses whole-genome sequencing to identify new genetic loci and structural variants associated with progressive supranuclear palsy, including novel signals in APOE and H1/H2 haplotype region variants.

Single-cell profiling of the human primary motor cortex in ALS and FTLD

The paper creates a single-cell atlas of the human primary motor cortex in ALS and FTLD, identifying transcriptional changes and molecular similarities between Betz cells and VENs.

Medically relevant tandem repeats in nanopore sequencing of control cohorts

The paper introduces PathSTR, a tool for analyzing tandem repeats using long-read sequencing, and demonstrates its application in a Myotonic Dystrophy type 1 case.

Scywalker: scalable end-to-end data analysis workflow for nanopore single-cell transcriptome sequencing

Scywalker provides a scalable analysis pipeline for nanopore single-cell transcriptome data, showing good correlation with short-read analyses and enabling isoform-level cell-type-specific expression identification.

PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons

The paper generates C9orf72 DPR knock-in mice and identifies an extracellular matrix signature in C9ALS/FTD that is conserved across species and protected by TGF-β1 and COL6A1.

NanoPack2: Population scale evaluation of long-read sequencing data

NanoPack2 provides tools for evaluating long-read sequencing data at scale, with updates to the NanoPack software suite.

Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer's Disease related proteins

This study performs a genome-wide association study of brain biochemical phenotypes in Alzheimer's patients, identifying novel genetic loci and highlighting distinct genetic architectures for AD-related proteins.

Identification of novel Alzheimer's disease genes co-expressed with TREM2

The paper identifies four genes, including two novel ones, co-expressed with TREM2 in Alzheimer's disease using whole-exome data from ADSP.

Analysis of brain atrophy and local gene expression in genetic frontotemporal dementia

The paper investigates the relationship between gene expression and brain atrophy in genetic frontotemporal dementia, finding correlations between atrophy patterns and specific gene sets related to vascular, glial, and neuronal functions.

Enrichment of rare protein truncating variants in amyotrophic lateral sclerosis patients

The paper identifies an enrichment of rare protein-truncating variants in ALS patients, highlighting novel genes like DNAJC7 and known ALS genes such as SOD1, NEK1, and FUS.

Systematic analysis of dark and camouflaged genes: disease-relevant genes hiding in plain sight

The paper identifies dark and camouflaged gene regions in the human genome, shows how long-read sequencing reduces their prevalence, and applies an algorithm to uncover disease-relevant variants in Alzheimer's Disease Sequencing Project data.

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

This paper introduces SuStaIn, a machine learning method that identifies disease subtypes and their temporal progression from cross-sectional data, improving prediction of diagnostic conversion in neurodegenerative diseases.

Long-read sequencing across the C9orf72 ‘GGGGCC’ repeat expansion: implications for clinical use and genetic discovery efforts in human disease

This study demonstrates that long-read sequencing can characterize the C9orf72 G4C2 repeat expansion in disease carriers, showing potential for clinical and genetic discovery applications.

Detection of long repeat expansions from PCR-free whole-genome sequence data

The paper introduces ExpansionHunter, a tool for detecting long repeat expansions from PCR-free WGS data, achieving high sensitivity and specificity in identifying pathogenic expansions.