Use of scREAD to explore and analyze single-cell and single-nucleus RNA-seq data for Alzheimer’s disease

Abstract

Summary Single-cell RNA-sequencing (scRNA-seq) and single-nucleus RNA-sequencing (snRNA-seq) studies have provided remarkable insights into understanding the molecular pathogenesis of Alzheimer's disease. We recently developed scREAD, a database to provide comprehensive analyses of all the existing AD scRNA-seq and snRNA-seq data from the public domain. Here, we report protocols for using the scREAD web interface and running the backend workflow locally. Our protocols enable custom analyses of AD single-cell and single-nucleus gene expression profiles. For complete details on the use and execution of this protocol, please refer to Jiang et al. (2020) .

Novel small molecules inhibit proteotoxicity and inflammation: Mechanistic and therapeutic implications for Alzheimer’s Disease, healthspan and lifespan- Aging as a consequence of glycolysis

“…It is therefore of great interest that CtBP2 gene expression is significantly elevated in almost every brain region examined in patients with AD, compared to controls, according to the AGORA database (Sugis et al, 2019). the most inhibited gene, significantly inhibited by 10/14 FDA-approved tricyclic congeners of GM310, was cysteine-rich protein 1 (CSRP1), which is conversely highly induced in all brain cell types, including microglia, in brains of Alzheimer’s patients, as indicated by the scREAD database [151], as well as in a mouse model of AD (Beckmann et al, 2020) and has been nominated as a potential target for AD by the agora.ampadportal.org (Ming et al, 2021). Of particular interest, the reversal of age-related human cardiovascular impairments by FOX03, the human analog of daf-16, appears to be mediated by inhibition of CSRP1 [152].…”

“…phenylbutyrate alone reversed the expression of 36% of the genes differentially expressed in microglia in AD [151]. Quetiapine combined with valproate, like phenylbutyrate an HDAC inhibitor, also improves symptoms in patients with AD [180].…”

“…The same combination is currently in clinical trials to treat AD, with promising results so far on surrogate measures https://www.amylyx.com/pipeline. It is also of some interest that, based on the CMAP database [141], phenylbutyrate alone reversed the expression of 36% of the genes differentially expressed in microglia in AD [151]. Quetiapine combined with valproate, like phenylbutyrate an HDAC inhibitor, also improves symptoms in patients with AD [180].…”

Decoding the Role of Astrocytes in the Entorhinal Cortex in Alzheimer’s Disease Using High-Dimensional Single-Nucleus RNA Sequencing Data and Next-Generation Knowledge Discovery Methodologies: Focus on Drugs and Natural Product Remedies for Dementia

“…ADRD contributes to the majority of dementia cases worldwide ( Winblad et al, 2016 ). Recent advances in genome sequencing technologies such as scRNA-Seq and snRNASeq are critical for deciphering the roles of heterogeneous cell populations in the brain at the single-cell level, and subsequent dissecting of these datasets using high throughput knowledge discovery platforms may provide clues as to why a particular group of cells is susceptible to AD and ADRD ( Jiang et al, 2020 ; Wu and Zhang, 2020 ; Wang et al, 2021 ). Here, snRNASeq datasets of astrocytes isolated from the entorhinal cortex region of AD patients and healthy brains were obtained and analyzed using scREAD web-tool.…”

“…Here, snRNASeq datasets of astrocytes isolated from the entorhinal cortex region of AD patients and healthy brains were obtained and analyzed using scREAD web-tool. scREAD includes 73 datasets from 16 studies, 10 brain regions, and 713,640 cells, and provides cell type and sub-cluster predictions, decipherment of DEGs, and discovery of cell type-specific regulons ( Jiang et al, 2020 ; Wu and Zhang, 2020 ; Wang et al, 2021 ).…”