Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reversion of Alzheimer’s disease signatures

ABSTRACT: Reversion of Alzheimer’s disease signatures

PROVIDER: PRJNA564801 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Reversion of Alzheimer’s disease signatures

Project description:Chemical Checker (CC) is a resource that provides processed, harmonized and integrated bioactivity data on 800,000 small molecules. In the CC, bioactivity data are expressed in a vector format, which naturally extends the notion of chemical similarity between compounds to similarities between bioactivity signatures of different kinds. We experimentally validate that CC signatures can be used to reverse and mimic biological signatures of disease models and genetic perturbations. We developed cellular models of Alzheimer’s disease (AD) by introducing familial AD (fAD) mutations into SH-SY5Y cells. Using CRISPR/Cas9-induced homology-directed repair, we obtained clones harboring the fAD PSEN1-M146V or the APP-V717F mutations. Three compounds (noscapine - 10 uM, palbociclib - 0.4 uM and AG-494 - 10uM) reverted fAD signatures. We confirmed that genes up-regulated in SH-SY5Y fAD mutants were indeed downregulated upon treatment with the drugs, and vice versa. Moreover, the three drug treatments significantly reverted a subset of genes strongly linked to AD, including the recovery of the expression levels of GRIN2D, a glutamate receptor involved in synaptic transmission and BIN1, a gene involved in synaptic vesicle endocytosis and strongly associated with AD risk.

2020-03-17 | GSE137202 | GEO

Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer’s disease

Project description:Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer’s disease

| PRJNA530780 | ENA

Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer’s disease

Project description:Tau aggregation in neurofibrillary tangles (NFTs) is closely associated with neurodegeneration and cognitive decline in Alzheimer’s disease (AD). However, the molecular signatures that distinguish between aggregation-prone and aggregation-resistant cell states are unknown. We developed methods for the high-throughput isolation and transcriptome profiling of single somas with NFTs fro¬m human AD brain, quantified the susceptibility of 20 neocortical subtypes for NFT formation and death, and identified both shared and cell-type-specific signatures. NFT-bearing neurons shared a marked upregulation of synaptic transmission-related genes, including a core set of 63 genes enriched for synaptic vesicle cycling. Oxidative phosphorylation and mitochondrial dysfunction were highly cell-type dependent. Apoptosis was only modestly enriched, and the susceptibilities of NFT-bearing and NFT-free neurons for death were highly similar. Our analysis suggests that NFTs represent cell-type-specific responses to stress and synaptic dysfunction. We provide a resource for biomarker discovery and the investigation of tau-dependent and tau-independent mechanisms of neurodegeneration.

2020-08-05 | GSE129308 | GEO

Identification and drug-induced reversion of molecular signatures of Alzheimer’s disease onset and progression in AppNL-G-F, AppNL-F, and 3xTg-AD mouse models

Project description:Identification and drug-induced reversion of molecular signatures of Alzheimer’s disease onset and progression in AppNL-G-F, AppNL-F, and 3xTg-AD mouse models

| PRJNA707405 | ENA

Histone H3 lysine 4 and 27 trimethylation signatures associated with human Alzheimer’s disease

Project description:Histone H3 lysine 4 and 27 trimethylation signatures associated with human Alzheimer’s disease

| PRJNA804862 | ENA

Gut microbiome alterations in Alzheimer’s disease

Project description:Gut microbiome alterations in Alzheimer’s disease

| PRJEB51982 | ENA

Project description:Sex-related differences in Alzheimer’s disease

| PRJNA839023 | ENA

Age, Sex and Alzheimer’s disease: a longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimer’s patients

Project description:Aging and sex are major risk factors for developing late-onset Alzheimer’s disease. Compared to men, women are not only nearly twice as likely to develop Alzheimer’s, but they also experience worse neuropathological burden and cognitive decline despite living longer with the disease. It remains unclear how and when sex differences in biological aging emerge and contribute to Alzheimer’s disease pathogenesis. We hypothesized that these differences lead to distinct molecular Alzheimer’s disease signatures in males and females, which could be harnessed for therapeutic and biomarker development. We aged male and female, 3xTg-AD and B6129 control mice across their respective lifespans while longitudinally collecting brain samples. We conducted RNA sequencing analysis on bulk brain tissue and examined differentially expressed genes between 3xTg-AD and B6129 samples and across ages in each sex. 3xTg-AD males experienced an accelerated upregulation of immune-related gene expression in the brain relative to females, especially in genes involved in complement system activation, suggesting distinct inflammatory disease trajectories between the sexes. Our data demonstrate that chronic inflammation and complement activation are associated with increased mortality, revealing that age-related changes in immune response act as a primary driver of sex differences in Alzheimer’s disease trajectories.

2024-07-08 | GSE254970 | GEO

Genome-wide survey of large rare copy number variations in Alzheimer’s disease among Caribbean Hispanics

Project description:Recently genome-wide association studies have identified significant association between Alzheimer’s disease and variations in CLU, PICALM, BIN1, CR1, MS4A4/MS4A6E, CD2AP, CD33, EPHA1 and ABCA7. However, the pathogenic variants in these loci have not yet been found. We conducted a genome-wide scan for large copy number variations (CNVs) in a dataset of Caribbean Hispanic origin (554 controls and 559 cases with late-onset Alzheimer’s disease) that was previously investigated in a SNP-based genome-wide association study using Illumina HumanHap 650Y platform. We ran four CNV calling algorithms and analyzed rare large CNVs (>100 Kb) to obtain high-confidence calls that were detected by at least two algorithms. In total, 734 such CNVs were observed in our dataset. Global burden analyses did not reveal significant differences between cases and controls in CNV rate, distribution of deletions or duplications, total or average CNV size; and number of genes affected by CNVs. However, we observed a nominal association between Alzheimer’s disease and a ~470 Kb duplication on chromosome15q11.2 (P=0.037). This duplication, encompassing up to five genes (TUBGCP5, CYFIP1, NIPA2, NIPA1 and WHAMML1) was present in 10 cases (2.6%) and 3 controls (0.8%). The dosage increase of CYFIP1 and NIPA1 genes was further confirmed by quantitative PCR. The current study did not detect CNVs (including common CNVs) that affect novel Alzheimer’s disease loci reported by large genome-wide association studies. However, since the array technology used in our study has limitations in detecting small CNVs, future studies must carefully assess novel AD associated genes for the presence of disease related CNVs. Case-control analysis, screening of large copy number variation in 559 Alzheimer cases and 554 control subjects of Caribbean Hispanic ancestry

2012-04-30 | E-GEOD-33528 | biostudies-arrayexpress

Methylomic signatures of tau and beta amyloid in transgenic mouse models of Alzheimer’s disease neuropathology

Project description:Methylomic signatures of tau and beta amyloid in transgenic mouse models of Alzheimer’s disease neuropathology

| PRJNA1033631 | ENA