ArticleThe Journal of clinical investigation2022
Alzheimer's disease and progressive supranuclear palsy share similar transcriptomic changes in distinct brain regions.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Pooled it
- Brain DNA methylomic analysis of frontotemporal lobar degeneration reveals OTUD4 in shared dysregulated signatures across pathological subtypes.Acta neuropathologica · 2023Pooled it
- Sphingolipid and ceramide associations with tau pathology vary across diverse ethnoracial groups in postmortem brain tissue.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- Brain multiomic profiling identifies tau-related transcriptomic dysregulation in Alzheimer's disease.Brain communications · 2026Article
- 4R-tau seeding activity reveals molecular subtypes in progressive supranuclear palsy.Nature communications · 2025Article
- Review
- Sphingolipid and ceramide associations with tau pathology vary across diverse ethnoracial groups in postmortem brain tissue.medRxiv : the preprint server for health sciences · 2025Article
- Characterizing the expression profile of 3R tau pathology in Pick's disease.Science advances · 2025Article
- Multi-region brain transcriptomic analysis of amyotrophic lateral sclerosis reveals widespread RNA alterations and substantial cerebellum involvement.Molecular neurodegeneration · 2025Article
- Characterization of Isolated Human Astrocytes from Aging Brain.International journal of molecular sciences · 2025Article
- Comparative brain metabolomics reveals shared and distinct metabolic alterations in Alzheimer's disease and progressive supranuclear palsy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Brain regions differences in amyloid-β and gene expression in early APP/PS1 mice and identification ofBiomolecules & biomedicine · 2024Article
- Bridging the gap: Multi-omics profiling of brain tissue in Alzheimer's disease and older controls in multi-ethnic populations.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Integrative proteomics identifies a conserved Aβ amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer's disease.Cell reports. Medicine · 2024Article
- Transcriptomic imputation of genetic risk variants uncovers novel whole-blood biomarkers of Parkinson's disease.NPJ Parkinson's disease · 2024Article
- Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations.bioRxiv : the preprint server for biology · 2024Article
- Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer's disease.Acta neuropathologica · 2024Article
- Cross species systems biology discovers glial DDR2, STOM, and KANK2 as therapeutic targets in progressive supranuclear palsy.Nature communications · 2023Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 1 country.
Funding
Abstract
Vast numbers of differentially expressed genes and perturbed networks have been identified in Alzheimer's disease (AD), however, neither disease nor brain region specificity of these transcriptome alterations has been explored. Using RNA-Seq data from 231 temporal cortex and 224 cerebellum samples from patients with AD and progressive supranuclear palsy (PSP), a tauopathy, we identified a striking correlation in the directionality and magnitude of gene expression changes between these 2 neurodegenerative proteinopathies. Further, the transcriptomic changes in AD and PSP brains ware highly conserved between the temporal and cerebellar cortices, indicating that highly similar transcriptional changes occur in pathologically affected and grossly less affected, albeit functionally connected, areas of the brain. Shared up- or downregulated genes in AD and PSP are enriched in biological pathways. Many of these genes also have concordant protein changes and evidence of epigenetic control. These conserved transcriptomic alterations of 2 distinct proteinopathies in brain regions with and without significant gross neuropathology have broad implications. AD and other neurodegenerative diseases are likely characterized by common disease or compensatory pathways with widespread perturbations in the whole brain. These findings can be leveraged to develop multifaceted therapies and biomarkers that address these common, complex, and ubiquitous molecular alterations in neurodegenerative diseases.
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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.