Transcriptomic analysis of the hippocampus in Alzheimer’s disease
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA767074 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16101430_1.fastq.gz | Fastqsanger.gz | |||
| SRR16101430_2.fastq.gz | Fastqsanger.gz | |||
| SRR16101431_1.fastq.gz | Fastqsanger.gz | |||
| SRR16101431_2.fastq.gz | Fastqsanger.gz | |||
| SRR16101432_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Purpose: The goal of this study is to compare NGS-derived transcriptome profiling (RNA-seq) in AD patients’ hippocampus. Methods: mRNA profiles of human hippocampus from AD patients and healthy controls were generated by deep sequencing, using Illumina GAIIx. Results: Using an optimized data analysis workflow, more than 20000 transcripts in hippocampus were detected. Top 6 genes were selected and related to “ion transport”. Correlation analysis demonstrated negative relationship of gene expression level with the neuropathologic changes.
2021-10-05 | GSE184942 | GEO
Project description:Transcriptomic profiling of sporadic Alzheimer’s disease patients
| PRJNA839035 | ENA
Project description:Hippocampus is a critical region involved in learning, memory and various brain disorders. The molecular diversity of various glial cells in the human hippocampus and their temporal changes over the postnatal life remain largely unknown. Here we performed single-nucleus RNA-sequencing to create a transcriptome atlas of the human hippocampus across the postnatal lifespan and in Alzheimer’s disease (AD). Detailed analyses of astrocytes, oligodendrocyte lineages, and microglia identified subpopulations with distinct transcriptomic signatures, transcription factor expression patterns, association with specific biological processes, and changes in their abundance with age. Enrichment analysis of brain disorder risk gene expression further implicates specific glial cells and subpopulations in various brain disorders. Furthermore, we identified dysregulated gene expression in specific glial subpopulations in the hippocampus of AD patients. Together, these data provide a rich resource and significantly extend our understanding of human glial cell diversity and their temporal distribution across the postnatal lifespan.
2022-08-26 | GSE199243 | GEO
Project description:Microglia, the brain’s principal immune cells, have been implicated in the pathogenesis of Alzheimer’s disease (AD), a condition shown to affect more females than males. Although sex differences in microglial function and transcriptomic programming have been described across development and in disease models of AD, no studies have comprehensively identified the sex divergences that emerge in the aging mouse hippocampus. Further, existing models of AD generally develop pathology (amyloid plaques and tau tangles) early in life and fail to recapitulate the aged brain environment associated with late-onset AD. Here, we examined and compared the transcriptomic and translatomic sex effects in young and old murine hippocampal microglia. Hippocampal tissue from C57BL6/N and microglial NuTRAP mice of both sexes were collected at young (5-6 month-old [mo]) and old (22-25 mo) ages. Cell sorting and affinity purification techniques were used to isolate the microglial transcriptome and translatome for RNA-sequencing and differential expression analyses. Flow cytometry, qPCR, and imaging approaches were used to confirm the transcriptomic findings. There were marginal sex differences identified in the young hippocampal microglia, with most differentially expressed genes (DEGs) restricted to the sex chromosomes. Both sex chromosomally- and autosomally-encoded sex differences emerged with aging. These sex DEGs identified at old age were primarily female-biased and enriched in senescent and disease-associated microglial signatures. Pathway analyses identified upstream regulators induced to a greater extent in females than in males, including inflammatory mediators IFNG, TNF, and IL1B, as well as AD-risk genes TREM2 and APP. These data suggest that female microglia adopt disease-associated and senescent phenotypes in the aging mouse hippocampus, even in the absence of disease pathology, to a greater extent than males. This sexually divergent microglial phenotype may explain the difference in susceptibility and disease progression in the case of AD pathology. Future studies will need to explore sex differences in microglial heterogeneity in response to AD pathology and determine how sex-specific regulators (i.e., sex chromosomal or hormonal) elicit these sex effects.
2023-08-18 | GSE233400 | GEO
Project description:Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer’s Disease
| PRJNA729525 | ENA
Project description:Transcriptomic signatures of oxytosis/ferroptosis are enriched in Alzheimer’s disease
| PRJNA1168515 | ENA
Project description:Microglia is dynamically reprogrammed according to the progression of Alzheimer’s disease (AD). However, clinical translation into biomarker development for functional change in microglia has not been achieved. Here, we find the close association of the metabolic reconfiguration of microglia with increased hippocampal glucose uptake, which can be noninvasively estimated by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). We found that increased FDG activity in the hippocampus of an AD mouse model depended on microglial uptake. Single-cell RNA-sequencing of the hippocampus showed the changes of glucose metabolism profiles including glucose transporters, glycolysis and oxidative phosphorylation mainly occurred in microglia. A subset of microglia with high glucose transporters with defective glycolysis and oxidative phosphorylation was increased according to disease progression. Furthermore, we also found a positive association between a soluble TREM2 of cerebrospinal fluid, a marker of microglial activation, and hippocampal FDG uptake as a human study. We identified a reconfiguration of microglial glucose metabolism in the hippocampus of AD and suggested a feasible imaging biomarker based on widely used FDG PET to reflect microglial metabolic profiles.
2021-09-08 | GSE150934 | GEO
Project description:Background: Major Depression (MD) is the most prevalent psychiatric disease in the population and is considered a prodromal stage of the Alzheimer’s disease (AD). Despite both diseases having a robust genetic component, the common transcriptomic signature remains unknown. Method: In this regard, we investigated the cognitive and emotional behavioural responses in 3- (n=16 per group) and 6-month-old (n=14 per group) in APP/PSEN1-Tg mutant mice, before -amyloid plaques were detected in comparison with non-transgenic mice. Then, we studied the deregulation of genes and pathways in prefrontal cortex, striatum, hippocampus and amygdala of mice at both ages, using transcriptomic and functional data analysis. Results: We found that depressive-like and anxiety-like behaviours, as well as memory impairments are already present at 3-month-old APP/PSEN1-Tg mutant mice together with the deregulation of several genes such as Ciart, Chrm5, Aldh1a, Grin3b, Nr1d1 and Mc4r, and gene sets, including components of the circadian rhythms, electronic transport chain, neuroinflammation and neurotransmission. Then, we extended these results to human data performing GSEA analysis using DisGeNET database, which is specific for diseases and disease-related phenotypes and provides translational support for common deregulated gene sets related to MD and AD. Conclusion: The present study shed further light on the genetic bases shared between MD and AD, illustrating a wide characterization from the behavioural to transcriptomic level in APP/PSEN1-Tg mutant mouse model. These findings could indicate that late MD could be an early manifestation of AD.
2022-01-17 | GSE167739 | GEO
Project description:Reversion of Alzheimer’s disease signatures
| PRJNA564801 | ENA
Project description:Alzheimer’s disease (AD) manifested before age 65 is commonly referred to as early-onset AD (EOAD). While the majority (> 90%) of EOAD cases are not caused by autosomal-dominant mutations in PSEN1, PSEN2, and APP, they do have a higher heritability (92–100%) than sporadic late-onset AD (LOAD, 70%). Although the endpoint clinicopathological changes, i.e., Aβ plaques, tau tangles, and cognitive decline, are common across EOAD and LOAD, the disease progression is highly heterogeneous. This heterogeneity, leading to temporally distinct age at onset (AAO) and stages of cognitive decline, may be caused by myriad combinations of distinct disease-associated molecular mechanisms. We and others have used transcriptome profiling in AD patient-derived neuron models of autosomal-dominant EOAD and sporadic LOAD to identify disease endotypes. Further, analyses of large postmortem brain cohorts demonstrate that only one-third of AD patients show hallmark disease endotypes like increased inflammation and decreased synaptic signaling. Areas of the brain less affected by AD pathology at early disease stages—such as the primary visual cortex—exhibit similar transcriptomic dysregulation as those regions traditionally affected and, therefore, may offer a view into the molecular mechanisms of AD without the associated inflammatory changes and gliosis induced by pathology. To this end, we analyzed AD patient samples from the primary visual cortex (19 EOAD, 20 LOAD) using transcriptomic signatures to identify patient clusters and disease endotypes. Interestingly, although the clusters showed distinct combinations and severity of endotypes, each patient cluster contained both EOAD and LOAD cases, suggesting that AAO may not directly correlate with the identity and severity of AD endotypes.
2022-10-12 | GSE203206 | GEO