Transcriptomic analysis of the hippocampus in Alzheimer’s disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE184942 | GEO | 2021/10/05
REPOSITORIES: GEO
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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:Unravel the mechanisms underlying brain aging and Alzheimer´s disease (AD) has been difficult because of complexity of the networks that drive these aging-related changes. Analysis of the gene expression in the brain is a valuable tool to study the function of the brain under normal and pathological conditions. Gene microarray technology allows massively parallel analysis of most genes expressed in a tissue, and therefore is an important research tool that potentially can provide the investigative power needed to address the complexity of brain aging and neurodegenerative processes. One of the reasons that account for the resistance of AD pathogenesis to analysis is that clinically normal subjects may exhibit considerable AD pathology, blurring criteria for distinguishing subjects with normal aging or AD. Here, we analyzed hippocampal and cortex frontal gene expression from 32 subjects separated in individuals presenting, 1) both pathologic and clinical AD (definitive AD); 2) AD pathology and normal clinic (pathologic AD); 3) cognitive impairment, without AD pathology (others dementias); and 4) no cognitive impairment, without AD pathology (normal individuals). Our results show that based on gene expression profile these individuals we could verify similarity between the definitive AD group and the group that only had AD-type pathology (pathologic AD). Specimens of hippocampus and cortex frontal used in this study were obtained at autopsy from 32 subjects. Neuropathology, specifically NFT and NP, was assessed in accordance to the Braak staging and CERAD scores, respectively. Based on pathologic and clinic criteria, subjects were categorized into four groups: 1) nine subjects with AD neuropathologic (Braak = IV / V / VI and CERAD ≠ 0) presenting cognitive impairment (CDR ≥ 1), termed “definitive AD” (dAD); 2) five subjects with AD neuropathologic (Braak = IV / V / VI and CERAD ≠ 0) and without cognitive impairment (CDR = 0), termed “pathologic AD” (pAD); 3) nine subjects without AD neuropathologic (Braak = 0 / I / II and CERAD ≠ C) presenting cognitive impairment (CDR ≥ 1), termed “other dementias” (OD); 4) - nine subjects without AD neuropathologic (Braak = 0 / I / II and CERAD ≠ C) and without cognitive impairment (CDR = 0), termed “normal” (N). RNA isolation and Amplification. From total RNA, a two-round linear amplification procedure (T7-based protocol) was carried out for all samples and for a pool of RNAs obtained from 15 distinct human cell lines used as reference. Labeled cDNA was generated in a reverse transcriptase reaction using amplified RNA (aRNA). Equal amounts of test and reference cDNA reverse color Cy-labeled aRNA targets were competitively hybridized against the cDNA probes in a customized cDNA platform with 4,608 ORESTES representing human genes. Dye-swap was performed for each sample as control for dye bias and used as replicate.
2013-01-11 | E-GEOD-13214 | biostudies-arrayexpress
Project description:To investigate the regulatory genes responsible for the neuropathology in AD, we performed microarray analysis with APPV717I-CT100 transgenic mice, an animal model of AD. We extracted total RNA of hippocampus in three brains of 11 month-old APPV717I-CT100 Tg mice. Total RNA was prepared from using Trizol reagent. Control vs APPV717I-CT100 Tg mice. Three hippocampus per array were used.
2010-09-28 | E-GEOD-18762 | biostudies-arrayexpress
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:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare transcriptome profiling (RNA-seq) of adult hippocampus from offspring from control and preeclampsia mother mice. Methods: Adult hippocampus RNA profiles of offspring from control and preeclampsia mother mice were generated by deep sequencing, in triplicate, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm9) and identified 16,014 transcripts in the adult hippocampus of offspring from control and preeclampsia mother mice with BWA workflow and 34,115 transcripts with TopHat workflow. R Conclusions: Our study represents the first detailed analysis of adult hippocampus transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of RNA content within tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.
2023-06-06 | GSE167194 | GEO
Project description:We addressed the integrated analysis of mRNA and miRNA expression levels of Tg6799 AD model mice at 4 month and 8 months of age. Total 8 gene cluster modules for co-expression network were predicted from transcriptome data and 6 modules were show relation with AD or aging. We constructed early stage AD network using data integration between mRNA and miRNA profiles and predicted miRNAs strongly involved in module regulation. We found that ARRDC3 showed AD mutation dependent changes of expression and was related metabolic dysfunction in early stage AD. These results demonstrate that candidate genes on the simultaneous profiling of mRNA and miRNA expressions in genome wide can be used for the understanding of non-coding RNA related gene expression in early stage AD. We suggested that our results could be future candidate to be developed as early biomarkers in progressive AD pathology. This result can be used for the further application in neurodegenerative diseases. Tg6799 transgenic mice were purchased from The Jackson Laboratory (USA) and were housed under a 12h light-dark cycle with free access to food and water. Female Tg6799 mice are maintained until 4 months and 8 months of age (for littermate control: LM and mutant subjects: MT). RNA samples were isolated from hippocampus of mice using TRI-Reagent (Sigma-Aldrich, St. Louis, MO) according to the manufacturer’s instructions. Gene expression was analyzed with GeneChip® Mouse Genome 430 2.0 Arrays (Affymetrix, Santa Clara, CA), which is comprised of over 45,000 probe sets representing approximately 28,700 well-characterized mouse genes. The Ion Total RNA-Seq Kit v2 (Lifetechnologies, USA) was used for the preparation of micro RNA libraries according to the manufacturer's instructions. Total numbers of subject used are as followed: 1) LM 4 months : MT 4 months : LM 8 months : MT 8 months (2:4:2:4) for screening mRMA and miRNA, 2) LM 4 months : MT 4 months : LM 8 months : MT 8 months (4:4:4:4) for expression verification. Tg6799 transgenic mice were purchased from The Jackson Laboratory (USA) and were housed under a 12h light-dark cycle with free access to food and water. Female Tg6799 mice are maintained until 4 months and 8 months of age (for littermate control: LM and mutant subjects: MT). RNA samples were isolated from hippocampus of mice using TRI-Reagent (Sigma-Aldrich, St. Louis, MO) according to the manufacturer’s instructions. Gene expression was analyzed with GeneChip® Mouse Genome 430 2.0 Arrays (Affymetrix, Santa Clara, CA), which is comprised of over 45,000 probe sets representing approximately 28,700 well-characterized mouse genes. The Ion Total RNA-Seq Kit v2 (Lifetechnologies, USA) was used for the preparation of micro RNA libraries according to the manufacturer's instructions. Total numbers of subject used are as followed: 1) LM 4 months : MT 4 months : LM 8 months : MT 8 months (2:4:2:4) for screening mRMA and miRNA, 2) LM 4 months : MT 4 months : LM 8 months : MT 8 months (4:4:4:4) for expression verification.
2013-12-01 | E-GEOD-52022 | biostudies-arrayexpress
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:We addressed the integrated analysis of mRNA and miRNA expression levels of Tg6799 AD model mice at 4 month and 8 months of age. Total 8 gene cluster modules for co-expression network were predicted from transcriptome data and 6 modules were show relation with AD or aging. We constructed early stage AD network using data integration between mRNA and miRNA profiles and predicted miRNAs strongly involved in module regulation. We found that ARRDC3 showed AD mutation dependent changes of expression and was related metabolic dysfunction in early stage AD. These results demonstrate that candidate genes on the simultaneous profiling of mRNA and miRNA expressions in genome wide can be used for the understanding of non-coding RNA related gene expression in early stage AD. We suggested that our results could be future candidate to be developed as early biomarkers in progressive AD pathology. This result can be used for the further application in neurodegenerative diseases. Tg6799 transgenic mice were purchased from The Jackson Laboratory (USA) and were housed under a 12h light-dark cycle with free access to food and water. Female Tg6799 mice are maintained until 4 months and 8 months of age (for littermate control: LM and mutant subjects: MT). RNA samples were isolated from hippocampus of mice using TRI-Reagent (Sigma-Aldrich, St. Louis, MO) according to the manufacturer’s instructions. Gene expression was analyzed with GeneChip® Mouse Genome 430 2.0 Arrays (Affymetrix, Santa Clara, CA), which is comprised of over 45,000 probe sets representing approximately 28,700 well-characterized mouse genes. The Ion Total RNA-Seq Kit v2 (Lifetechnologies, USA) was used for the preparation of micro RNA libraries according to the manufacturer's instructions. Total numbers of subject used are as followed: 1) LM 4 months : MT 4 months : LM 8 months : MT 8 months (2:4:2:4) for screening mRMA and miRNA, 2) LM 4 months : MT 4 months : LM 8 months : MT 8 months (4:4:4:4) for expression verification.
2013-12-01 | E-GEOD-52023 | biostudies-arrayexpress
Project description:To investigate the regulatory genes responsible for the neuropathology in AD, we performed microarray analysis with APPV717I-CT100 transgenic mice, an animal model of AD. We extracted total RNA of hippocampus in three brains of 11 month-old APPV717I-CT100 Tg mice. Total RNA was prepared from using Trizol reagent.
2010-09-28 | GSE18762 | GEO
Project description:Human brain tissue was obtained from the New Zealand Brain Bank from donors with Alzheimer's disease (AD) or age-matched controls (n=9/group). Mean post mortem delays were ~12h. Six distinct brain regions were dissected, Hippocampus, Cingulate Gyrus, Entorhinal Cortex (severely affected), Motor and Sensory Cortex (less affected) and Cerebellum (spared). Protein was extracted from each sample and, each region was analysed independently. For each region, samples were divided into 3 sets of 3 cases and 3 controls and assigned to an iTRAQ 8 plex, alongside two aliquots of a pooled QC sample. Samples were digested, iTRAQ labelled and analysed. For each region, between 3000 and 4200 proteins were compared between AD and control, identifying a series of known and novel protein expression changes associated with the progression of AD.
2019-02-15 | PXD008739 | Pride