Aging and neurodegenerative disease are characterized by genomic instability in neurons, including aberrant activation and mobilization of transposable elements (TEs). Integrating studies of human postmortem brain tissue and Drosophila melanogaster models, we investigate TE activation in association with Tau pathology in Alzheimer's disease (AD). Leveraging RNA sequencing from 636 human brains, we discover differential expression for several retrotransposons in association with neurofibrillary tangle burden and highlight evidence for global TE transcriptional activation among the long interspersed nuclear element 1 and endogenous retrovirus clades. In addition, we detect Tau-associated, active chromatin signatures at multiple HERV-Fc1 genomic loci. To determine whether Tau is sufficient to induce TE activation, we profile retrotransposons in Drosophila expressing human wild-type or mutant Tau throughout the brain. We discover heterogeneous response profiles, including both age- and genotype-dependent activation of TE expression by Tau. Our results implicate TE activation and associated genomic instability in Tau-mediated AD mechanisms.
The Drosophila melanogaster gypsy transposable element encodes putative gene products homologous to retroviral proteins.
Characterization of the low-copy HERV-Fc family: evidence for recent integrations in primates of elements with coding envelope genes
Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination
Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis
Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells
DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88
Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci
TDP-1, the Caenorhabditis elegans ortholog of TDP-43, limits the accumulation of double-stranded RNA
Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila
The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis
Somatic LINE-1 retrotransposition in cortical neurons and non-brain tissues of Rett patients and healthy individuals
Cellular labeling of endogenous retrovirus replication (CLEVR) reveals de novo insertions of the gypsy retrotransposable element in cell culture and in both neurons and glial cells of aging fruit flies
Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression
GeneTEFlow: A Nextflow-based pipeline for analysing gene and transposable elements expression from RNA-Seq data
Drosophila melanogaster as a Model to Study the Multiple Phenotypes, Related to Genome Stability of the Fragile-X Syndrome
Analysis of repetitive element expression in the blood and skin of patients with Parkinson's disease identifies differential expression of satellite elements
An Increased Burden of Highly Active Retrotransposition Competent L1s Is Associated with Parkinson's Disease Risk and Progression in the PPMI Cohort.
Decoding the Role of Satellite DNA in Genome Architecture and Plasticity-An Evolutionary and Clinical Affair
Genomic Indexing by Somatic Gene Recombination of mRNA/ncRNA - Does It Play a Role in Genomic Mosaicism, Memory Formation, and Alzheimer's Disease?
TDP-43 prevents retrotransposon activation in the Drosophila motor system through regulation of Dicer-2 activity.
Transposable elements, circular RNAs and mitochondrial transcription in age-related genomic regulation.
Technical considerations in detection of HERV-K in amyotrophic lateral sclerosis: selection of controls and the perils of qPCR
Genome-wide identification of genic and intergenic neuronal DNA regions bound by Tau protein under physiological and stress conditions
Environmentally-Induced Transgenerational Epigenetic Inheritance: Implication of PIWI Interacting RNAs
Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development.
Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors
Transposon expression in the Drosophila brain is driven by neighboring genes and diversifies the neural transcriptome.
Emerging role of AMPA receptor subunit GluA1 in synaptic plasticity: Implications for Alzheimer's disease
Presymptomatic Increase of an Extracellular RNA in Blood Plasma Associates with the Development of Alzheimer's Disease.
G-quadruplexes originating from evolutionary conserved L1 elements interfere with neuronal gene expression in Alzheimer's disease.
Alzheimer's Disease: RNA Sequencing
RNA sequencing studies have shed light on the genetic and molecular mechanisms related to the pathophysiology of Alzheimer's disease (AD). This feed follows papers using RNA sequencing technologies in Alzheimer's research.
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Alzheimer's Disease: Transcription
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