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High-resolution omics of vascular ageing and inflammatory pathways in neurodegeneration

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2024)

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Functional characterization of the dural sinuses as a neuroimmune interface

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Multimodal single-cell/nucleus RNA sequencing data analysis uncovers molecular networks between disease-associated microglia and astrocytes with implications for drug repurposing in Alzheimer's disease

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Single-cell epigenomics reveals mechanisms of human cortical development

Ryan S. Ziffra et al.

Summary: During mammalian development, differences in chromatin state play a crucial role in cell fate specification and defining cell identity in the developing brain. Through studying chromatin accessibility patterns, it was found that cerebral organoids recapitulate most cell-type-specific enhancer accessibility patterns but lack some open chromatin regions found in vivo. Systematic comparison of chromatin accessibility across brain regions revealed unexpected diversity among neural progenitor cells and highlighted the role of retinoic acid signaling in neuronal lineage specification in the prefrontal cortex.

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DNA methylation atlas of the mouse brain at single-cell resolution

Hanqing Liu et al.

Summary: The study comprehensively assessed the epigenomes of different cell types in the mouse brain, revealing the diversity and spatial organization of cell types, as well as the repetitive usage of regulators for distinguishing cell subtypes. By constructing an artificial neural network model, it is possible to accurately predict the cell type and spatial location of individual neurons in the brain.

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Article Biochemical Research Methods

Joint probabilistic modeling of single-cell multi-omic data with totalVI

Adam Gayoso et al.

Summary: totalVI is a framework for end-to-end joint analysis of CITE-seq data which probabilistically represents data as a composite of biological and technical factors, providing a cohesive solution for common analysis tasks. It demonstrates strong performance in tasks such as dimensionality reduction, dataset integration, correlation estimation, and differential expression testing.

NATURE METHODS (2021)

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Oligodendrocyte precursor cell specification is regulated by bidirectional neural progenitor-endothelial cell crosstalk

Isidora Paredes et al.

Summary: Bidirectional crosstalk between neural and vascular compartments plays a critical role in oligodendrocyte precursor cell specification, with neural progenitor cells expressing angiopoietin-1 and endothelial cells producing transforming growth factor beta 1 in response. This collaboration demonstrates the complex relationship between NPCs and the vasculature in regulating oligodendrogenesis.

NATURE NEUROSCIENCE (2021)

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CD4+ T cells contribute to neurodegeneration in Lewy body dementia

David Gate et al.

Summary: The mechanism of T cell trafficking in LBD remains unclear. However, the study found that up-regulated expression of CXCR4 and IL-17A in CD4(+) T cells in CSF of LBD patients is associated with CXCL12 levels and neuroaxonal damage, suggesting that CXCR4-CXCL12 signaling may be a potential target for inhibiting pathological T cell activity in LBD.

SCIENCE (2021)

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Article Multidisciplinary Sciences

A practical solution to pseudoreplication bias in single-cell studies

Kip D. Zimmerman et al.

Summary: It has been found that single-cell data have a hierarchical structure that many current methods do not address, leading to biased inference and inflated error rates. The authors propose applying generalized linear mixed models to properly account for the correlation structure among cells within an individual.

NATURE COMMUNICATIONS (2021)

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Article Clinical Neurology

Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment

Claudiaf Cicognola et al.

Summary: Plasma GFAP can detect AD pathology in patients with MCI and predict conversion to AD dementia, showing potential clinical utility.

ALZHEIMERS RESEARCH & THERAPY (2021)

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Article Genetics & Heredity

DNA Methylation and Expression Profiles of Whole Blood in Parkinson's Disease

Adrienne R. Henderson et al.

Summary: Parkinson's disease (PD) is the second most common age-related neurodegenerative disease, diagnosed at advanced stages by motor deficits. Aberrant epigenetic modifications are detectable in blood and our study found differentially expressed genes (DEGs) and methylated regions (DMRs) in PD patients compared to healthy controls. Identified patterns of altered disease-specific DNA methylation and associated gene expression in whole blood provide a foundation for potential PD biomarkers.

FRONTIERS IN GENETICS (2021)

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Article Clinical Neurology

Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer's disease

Joana B. Pereira et al.

Summary: The study suggests that plasma GFAP concentration is associated with brain amyloid-beta pathology but not tau aggregation in Alzheimer's disease. This indicates that plasma GFAP may be incorporated into current hypothetical models of Alzheimer's disease pathogenesis and used as a non-invasive tool to detect early astrocytosis.

BRAIN (2021)

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Article Biochemistry & Molecular Biology

Molecular diversity of diencephalic astrocytes reveals adult astrogenesis regulated by Smad4

Stefanie Ohlig et al.

Summary: Astrocytes exhibit diverse gene expression states related to distinct functions, with some subsets being more widespread while others are regionally restricted. The study also reveals the novel concept of low-level proliferation of astrocytes in the adult diencephalon, with Smad4 identified as a key regulator.

EMBO JOURNAL (2021)

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Article Endocrinology & Metabolism

Integrative analysis of the human brain mural cell transcriptome

Benjamin D. Gastfriend et al.

Summary: This study utilized multiple independent human brain single-cell RNA sequencing datasets to construct a transcriptomic database of human brain mural cells, with key findings validated by RNA fluorescence in situ hybridization. The research contributes to improving knowledge about the molecular constituents of human brain mural cells, serves as a resource for generating hypotheses about their function, and will facilitate comparative evaluation of animal and in vitro models.

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM (2021)

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Review Immunology

Microglia in Alzheimer's disease at single-cell level. Are there common in humans and mice?

Yun Chen et al.

Summary: Alzheimer's disease is characterized by the activation of microglia in response to amyloid beta peptides and tau aggregates, leading to the conversion of homeostatic microglia into disease-associated microglia. Different populations of reactive microglia have been identified, suggesting that microglia play a critical role in disease progression. Further research into the impact of microglia in AD pathogenesis is needed to better understand the parallels and discrepancies between human and mouse models.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Clinical Neurology

Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group

Bruno Dubois et al.

Summary: The use of biomarkers in the diagnosis of Alzheimer's disease has limitations and should be used cautiously in a clinical setting, restricted to individuals with specific phenotypes and positive biomarkers. Biomarker-positive cognitively unimpaired individuals should be considered at-risk for progression to Alzheimer's disease.

LANCET NEUROLOGY (2021)

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Article Genetics & Heredity

Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer's disease

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Summary: An integrative analysis of single-nucleus assay for transposase-accessible chromatin with sequencing and RNA sequencing in normal and Alzheimer's disease brain tissue reveals cell-type-specific cis-regulatory elements and candidate target genes. The study highlights the dynamic gene-regulatory landscape of the brain, identifying disease-related regulatory modules and transcription factors in specific cell types, demonstrating the utility of a multi-omic single-nucleus approach.

NATURE GENETICS (2021)

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Article Genetics & Heredity

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

Douglas P. Wightman et al.

Summary: This study identified seven new genetic loci associated with Alzheimer's disease through a genome-wide association study, implicating microglia and immune cells in late-onset disease. The research highlights the relevance of microglia, immune cells, and protein catabolism to late-onset Alzheimer's disease, while prioritizing previously unidentified genes for further investigation. The results are expected to contribute to larger meta-analyses to uncover additional genetic variants affecting Alzheimer's pathology.

NATURE GENETICS (2021)

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Article Neurosciences

Neuroinflammatory astrocyte subtypes in the mouse brain

Philip Hasel et al.

Summary: This study investigated the transcriptome changes of mouse cortical astrocytes after an acute inflammatory stimulus, revealing rapid and drastic changes over time. By sequencing thousands of astrocytes at single-cell resolution, it was shown that inflammation causes a widespread response with distinct subtypes undergoing inflammatory transitions with defined transcriptomic profiles. Spatial transcriptomics and in situ hybridization were used to attribute specific inflammation-induced reactive astrocyte sub-states to certain brain regions.

NATURE NEUROSCIENCE (2021)

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Article Multidisciplinary Sciences

Tissue-specific 5-hydroxymethylcytosine landscape of the human genome

Bo He et al.

Summary: 5hmC in human tissues shows tissue-specific patterns that may affect tissue-specific gene expression networks and are associated with specific single-nucleotide polymorphisms and diseases.

NATURE COMMUNICATIONS (2021)

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Article Clinical Neurology

Transcriptomic analysis of human brains with Alzheimer's disease reveals the altered expression of synaptic genes linked to cognitive deficits

Jamal B. Williams et al.

Summary: The downregulation of synaptic genes in the prefrontal cortex of Alzheimer's disease patients may contribute to cognitive deficits, with these lost synaptic genes encoding hub proteins necessary for cognitive stability. This study has identified potential molecular targets for therapeutic intervention of cognitive decline associated with Alzheimer's disease.

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ELIFE (2017)

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