Publications by authors named "V Haroutunian"
Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. This study presents a comprehensive single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.
View Article and Find Full Text PDFThe complex roles of myeloid cells, including microglia and perivascular macrophages, are central to the neurobiology of Alzheimer's disease (AD), yet they remain incompletely understood. Here, we profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 unique donors covering the human lifespan and varying degrees of AD neuropathology. We delineated 13 transcriptionally distinct myeloid subtypes organized into 6 subclasses and identified AD-associated adaptive changes in myeloid cells over aging and disease progression.
View Article and Find Full Text PDFArticle Synopsis
- Parkinson's Disease (PD) is a serious brain disorder affecting over 1% of people over 60, leading to issues with movement and thinking, but its exact causes are still unclear.
- To investigate the complexity of PD, researchers conducted single-nucleus RNA sequencing and whole-genome sequencing on 100 postmortem samples, selecting cases that represent varying stages and symptoms of the disease.
- The resulting dataset, created with high standards of quality control, is freely available on the AMP PD Knowledge Platform, facilitating research into the molecular mechanisms of PD and potentially helping to improve treatment options.
Brain region- and cell-specific transcriptomic and epigenomic features are associated with heritability for neuropsychiatric traits, but a systematic view, considering cortical and subcortical regions, is lacking. Here, we provide an atlas of chromatin accessibility and gene expression profiles in neuronal and non-neuronal nuclei across 25 distinct human cortical and subcortical brain regions from 6 neurotypical controls. We identified extensive gene expression and chromatin accessibility differences across brain regions, including variation in alternative promoter-isoform usage and enhancer-promoter interactions.
View Article and Find Full Text PDFIntroduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non-Hispanic White (NHW) populations. Here we provide an extensive survey of the proteomic landscape of AD across diverse racial/ethnic groups.
Methods: Two cortical regions, from multiple centers, were harmonized by uniform neuropathological diagnosis.