ArticleJournal of Alzheimer's disease : JAD2016
Protein Kinase Activity Decreases with Higher Braak Stages of Alzheimer's Disease Pathology.
Article in Journal of Alzheimer's disease : JAD, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Association between thyroid function and Alzheimer's disease: A systematic review.Metabolic brain disease · 2021Pooled it
- A meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex.Nature communications · 2021Pooled it
- Zebrafish frk Gene Knockout Shows Social Impairments Relevant to Autism and Delays Brain Development by Increasing Cell Proliferation.Autism research : official journal of the International Society for Autism Research · 2026Article
- The J bs-5YP peptide can alleviate dementia in senile mice by restoring the transcription of Slc40a1 to secrete the excessive iron from brain.Journal of advanced research · 2025Article
- Omics-derived biological modules reflect metabolic brain changes in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- A novel insight into neurological disorders through HDAC6 protein-protein interactions.Scientific reports · 2024Article
- Involvement of Endolysosomes and Aurora Kinase A in the Regulation of Amyloid β Protein Levels in Neurons.International journal of molecular sciences · 2024Article
- Predicting cognitive dysfunction and regional hubs using Braak staging amyloid-beta biomarkers and machine learning.Brain informatics · 2023Article
- Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer's Disease.Life (Basel, Switzerland) · 2023Article
- Genetic control of RNA editing in neurodegenerative disease.Briefings in bioinformatics · 2023Article
- The gene expression patterns as surrogate indices of pH in the brain.Frontiers in psychiatry · 2023Article
- ExonSkipAD provides the functional genomic landscape of exon skipping events in Alzheimer's disease.Briefings in bioinformatics · 2021Article
- A multifactorial model of pathology for age of onset heterogeneity in familial Alzheimer's disease.Acta neuropathologica · 2021Article
- KRSA: An R package and R Shiny web application for an end-to-end upstream kinase analysis of kinome array data.PloS one · 2021Article
- Phosphorylated Aβ peptides in human Down syndrome brain and different Alzheimer's-like mouse models.Acta neuropathologica communications · 2020Article
- Article
- Inactive immune pathways in triple negative breast cancers that showed resistance to neoadjuvant chemotherapy as inferred from kinase activity profiles.Oncotarget · 2018Article
- The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease.The Journal of pathology · 2018Article
- Kinomics toolbox-A web platform for analysis and viewing of kinomic peptide array data.PloS one · 2018Article
- Integrative Analysis of Hippocampus Gene Expression Profiles Identifies Network Alterations in Aging and Alzheimer's Disease.Frontiers in aging neuroscience · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is characterized by a long pre-clinical phase (20-30 years), during which significant brain pathology manifests itself. Disease mechanisms associated with pathological hallmarks remain elusive. Most processes associated with AD pathogenesis, such as inflammation, synaptic dysfunction, and hyper-phosphorylation of tau are dependent on protein kinase activity. The objective of this study was to determine the involvement of protein kinases in AD pathogenesis. Protein kinase activity was determined in postmortem hippocampal brain tissue of 60 patients at various stages of AD and 40 non-demented controls (Braak stages 0-VI) using a peptide-based microarray platform. We observed an overall decrease of protein kinase activity that correlated with disease progression. The phosphorylation of 96.7% of the serine/threonine peptides and 37.5% of the tyrosine peptides on the microarray decreased significantly with increased Braak stage (p-value <0.01). Decreased activity was evident at pre-clinical stages of AD pathology (Braak I-II). Increased phosphorylation was not observed for any peptide. STRING analysis in combination with pathway analysis and identification of kinases responsible for peptide phosphorylation showed the interactions between well-known proteins in AD pathology, including the Ephrin-receptor A1 (EphA1), a risk gene for AD, and sarcoma tyrosine kinase (Src), which is involved in memory formation. Additionally, kinases that have not previously been associated with AD were identified, e.g., protein tyrosine kinase 6 (PTK6/BRK), feline sarcoma oncogene kinase (FES), and fyn-associated tyrosine kinase (FRK). The identified protein kinases are new biomarkers and potential drug targets for early (pre-clinical) intervention.
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