Synapse-centered novel omics targets in Alzheimer’s disease - miRNA
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PROVIDER: PRJNA1159361 | ENA |
REPOSITORIES: ENA
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Project description:Synapse-centered novel omics targets in Alzheimer’s disease
| PRJNA1158813 | ENA
Project description:Synapse dysfunction is an early event of Alzheimer’s disease (AD). It is caused by multiple cellular and pathological factors such as Amyloid beta, p-tau, inflammation, and aging. However, the exact molecular mechanism of synapse dysfunction in AD is largely unknown. Therefore, to understand the molecular basis of synapse dysfunction in AD, we conducted a high throughput multi-omics analysis of the synaptosome fraction in postmortem brain samples from AD patients and cognitively normal individuals. First, microRNA and mRNA HiSeq analysis were performed on the synaptosomes extracted from the postmortem brains of unaffected control (UC) individuals and AD patients. Next, we conducted the mass spectrometry analysis of synaptosomal proteins in the same sample group of HC and AD. The transcriptomic and proteomic profiling of synaptosome showed the significant deregulation of miRNA, mRNA and protein signatures in AD vs HC. Further, we used an integrated transcriptomic and proteomic approach to understand the molecular interactions of deregulated synapse miRNAs, mRNAs, and proteins in the same samples of AD and HC. Multi-omics integration analysis of synapse miRNAs-mRNAs-proteins revealed the involvement of omics targets in several biological processes and molecular functions such as signal transduction, protein binding, GABAergic synapse, and synaptic vesicle cycle, etc. Our study unveiled synapse-centered novel omics candidates that could be potential therapeutic targets to restore synapse dysfunction in AD.
2025-09-09 | GSE276756 | GEO
Project description:Synapse dysfunction is an early event of Alzheimer’s disease (AD). It is caused by multiple cellular and pathological factors such as Amyloid beta, p-tau, inflammation, and aging. However, the exact molecular mechanism of synapse dysfunction in AD is largely unknown. Therefore, to understand the molecular basis of synapse dysfunction in AD, we conducted a high throughput multi-omics analysis of the synaptosome fraction in postmortem brain samples from AD patients and cognitively normal individuals. First, microRNA and mRNA HiSeq analysis were performed on the synaptosomes extracted from the postmortem brains of unaffected control (UC) individuals and AD patients. Next, we conducted the mass spectrometry analysis of synaptosomal proteins in the same sample group of HC and AD. The transcriptomic and proteomic profiling of synaptosome showed the significant deregulation of miRNA, mRNA and protein signatures in AD vs HC. Further, we used an integrated transcriptomic and proteomic approach to understand the molecular interactions of deregulated synapse miRNAs, mRNAs, and proteins in the same samples of AD and HC. Multi-omics integration analysis of synapse miRNAs-mRNAs-proteins revealed the involvement of omics targets in several biological processes and molecular functions such as signal transduction, protein binding, GABAergic synapse, and synaptic vesicle cycle, etc. Our study unveiled synapse-centered novel omics candidates that could be potential therapeutic targets to restore synapse dysfunction in AD.
2025-09-10 | GSE276898 | GEO
Project description:Synapse dysfunction is an early event of Alzheimer’s disease (AD). It is caused by multiple cellular and pathological factors such as Amyloid beta, p-tau, inflammation, and aging. However, the exact molecular mechanism of synapse dysfunction in AD is largely unknown. Therefore, to understand the molecular basis of synapse dysfunction in AD, we conducted a high throughput multi-omics analysis of the synaptosome fraction in postmortem brain samples from AD patients and cognitively normal individuals. First, microRNA and mRNA HiSeq analysis were performed on the synaptosomes extracted from the postmortem brains of unaffected control (UC) individuals and AD patients. Next, we conducted the mass spectrometry analysis of synaptosomal proteins in the same sample group of HC and AD. The transcriptomic and proteomic profiling of synaptosome showed the significant deregulation of miRNA, mRNA and protein signatures in AD vs HC. Further, we used an integrated transcriptomic and proteomic approach to understand the molecular interactions of deregulated synapse miRNAs, mRNAs, and proteins in the same samples of AD and HC. Multi-omics integration analysis of synapse miRNAs-mRNAs-proteins revealed the involvement of omics targets in several biological processes and molecular functions such as signal transduction, protein binding, GABAergic synapse, and synaptic vesicle cycle, etc. Our study unveiled synapse-centered novel omics candidates that could be potential therapeutic targets to restore synapse dysfunction in AD.
2025-10-27 | PXD055784 | Pride
Project description:AETA peptide contributes to Alzheimer’s disease signature of synapse dysfunction
| PRJNA1470672 | ENA
Project description:Alzheimer’s disease (AD), the leading cause of dementia, is characterized by early synaptic dysfunction that precedes overt cognitive decline. While amyloid-β and Tau remain central to AD pathogenesis, molecular triggers of synapse weakening remain unclear. Here, we investigated AETA, a novel brain-secreted peptide derived from amyloid precursor protein (APP), as a potential mediator of synapse dysfunction in AD. We previously identified AETA as a unique modulator of NMDA receptor activity in the healthy brain; however, its role in AD etiology was yet to be explored. Post-mortem analyses of human hippocampal and prefrontal cortex tissues revealed significantly elevated AETA levels in AD patients, particularly in females. To further explore the contribution of AETA to AD synaptic pathology, we analyzed a new mouse model, the AETA-m mouse, exhibiting chronically increased brain AETA expression. Hippocampi of female AETA-m mice display an increase in the number of astrocyte and microglia, but no overt neuroinflammation. RNA sequencing of female AETA-m hippocampi revealed alterations in synaptic gene expression that closely paralleled those observed in vulnerable human AD brain regions, most notably in the hippocampus. These two phenotypes were absent in males. Functionally, hippocampal neurons from AETA-m mice displayed impaired NMDA receptor signaling, dendritic spine loss, and memory deficits especially in females, mirroring early AD-associated synaptic dysfunction. Together, these findings identify AETA as a novel key contributor of synaptic vulnerability in AD and associated memory processing, especially in females. Targeting AETA signaling may, therefore, offer new therapeutic avenues for preventing or mitigating synaptic and cognitive decline in AD.
2026-06-10 | GSE333329 | GEO
Project description:We profiled REST targets in WT mice, as well as the Alzheimer’s disease 3xTg mouse model, to gain insight into the regulation of physiological pathways by REST, as well as the altered REST cistrome in Alzheimer’s disease.
2022-01-29 | GSE195446 | GEO
Project description:Identification of pathological pathways centered on circRNA dysregulation associated with irreversible progression of Alzheimer’s disease [5xFADHippocampus]
| PRJNA1138662 | ENA
Project description:Identification of pathological pathways centered on circRNA dysregulation associated with irreversible progression of Alzheimer’s disease [circGigyf2KD]
| PRJNA1138661 | ENA
Project description:Although circRNA abnormalities are found in Alzheimer’s disease (AD) postmortem brains, whether and how altered circRNA landscape lead to pathological gene network changes during AD progression remain undefined. Employing our recently published experimental and computational approaches, we found genome-wide dysregulated circRNA expression and disrupted functional cooperation of circRNAs in sponging microRNAs (miRNAs) and RNA-binding proteins (RBPs) during early pathogenic progression in a mouse AD model. In addition, we identified AD progression-associated mouse circRNAs that are conserved and affected in AD patients, which underlie malfunction of downstream microRNAs and RBPs in AD brains. An exemplar circRNA is circGigyf2, which progressively declines along with AD pathogenic severity. Furthermore, we identified AD pathological pathways centered on circGigyf2, including upstream RBPs that control circGigyf2 biogenesis and downstream miRNA-mRNA and RBP-mRNA axis regulated by circGigyf2, all affected in AD patients. Our discoveries provide strong evidence suggesting the contribution of circRNA abnormality in early AD pathogenesis.
2024-10-22 | GSE236683 | GEO