ArticleBrain : a journal of neurology2018
The human brainome: network analysis identifies HSPA2 as a novel Alzheimer’s disease target.
Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.Genome biology · 2025Pooled it
- Chromosome X-wide association study in case control studies of pathologically confirmed Alzheimer's disease in a European population.Translational psychiatry · 2024Pooled it
- Application of the Allen Human Brain Atlas in Alzheimer's disease and Parkinson's disease.Translational neurodegeneration · 2026Review
- Identification of important candidate genes in minks with self-biting behaviour using weighted gene coexpression network analysis.BMC genomics · 2026Article
- A Bioinformatic Analysis of BAG Protein Interactors and Pathways in Alzheimer's and Parkinson's Disease.Journal of molecular neuroscience : MN · 2026Review
- Article
- Changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer's disease.Scientific reports · 2024Article
- The Human Brainome: changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer's disease.Research square · 2023Article
- Predictive network analysis identifies JMJD6 and other potential key drivers in Alzheimer's disease.Communications biology · 2023Article
- Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- What does heritability of Alzheimer's disease represent?PloS one · 2023Article
- AI-DrugNet: A network-based deep learning model for drug repurposing and combination therapy in neurological disorders.Computational and structural biotechnology journal · 2023Article
- Identification of candidate biomarkers and pathways associated with type 1 diabetes mellitus using bioinformatics analysis.Scientific reports · 2022Article
- Culture shock: microglial heterogeneity, activation, and disrupted single-cell microglial networks in vitro.Molecular neurodegeneration · 2022Article
- HSPA1A, HSPA2, and HSPA8 Are Potential Molecular Biomarkers for Prognosis among HSP70 Family in Alzheimer's Disease.Disease markers · 2022Article
- Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE ε2 protective effect in Alzheimer disease.Molecular psychiatry · 2021Article
- Integration of peripheral transcriptomics, genomics, and interactomics following trauma identifies causal genes for symptoms of post-traumatic stress and major depression.Molecular psychiatry · 2021Observational
- Enhancing Top-Down Proteomics of Brain Tissue with FAIMS.Journal of proteome research · 2021Article
- Evolutionary conservation and divergence of the human brain transcriptome.Genome biology · 2021Article
- Construction of Unified Human Antimicrobial and Immunomodulatory Peptide Database and Examination of Antimicrobial and Immunomodulatory Peptides in Alzheimer's Disease Using Network Analysis of Proteomics Datasets.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
37 authors at 20 institutions in 3 countries.
Funding
Abstract
Our hypothesis is that changes in gene and protein expression are crucial to the development of late-onset Alzheimer’s disease. Previously we examined how DNA alleles control downstream expression of RNA transcripts and how those relationships are changed in late-onset Alzheimer’s disease. We have now examined how proteins are incorporated into networks in two separate series and evaluated our outputs in two different cell lines. Our pipeline included the following steps: (i) predicting expression quantitative trait loci; (ii) determining differential expression; (iii) analysing networks of transcript and peptide relationships; and (iv) validating effects in two separate cell lines. We performed all our analysis in two separate brain series to validate effects. Our two series included 345 samples in the first set (177 controls, 168 cases; age range 65–105; 58% female; KRONOSII cohort) and 409 samples in the replicate set (153 controls, 141 cases, 115 mild cognitive impairment; age range 66–107; 63% female; RUSH cohort). Our top target is heat shock protein family A member 2 (HSPA2), which was identified as a key driver in our two datasets. HSPA2 was validated in two cell lines, with overexpression driving further elevation of amyloid-β40 and amyloid-β42 levels in APP mutant cells, as well as significant elevation of microtubule associated protein tau and phosphorylated-tau in a modified neuroglioma line. This work further demonstrates that studying changes in gene and protein expression is crucial to understanding late onset disease and further nominates HSPA2 as a specific key regulator of late-onset Alzheimer’s disease processes.10.1093/brain/awy215_video1awy215media15824729224001.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.