ArticleNeuropathology and applied neurobiology2021
G protein-coupled receptor kinases are associated with Alzheimer's disease pathology.
Article in Neuropathology and applied neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 30 citations in OpenAlex.
- Post-translational modifications in the brain are critical contributors to Alzheimer's disease neuropathology and cognitive decline.bioRxiv : the preprint server for biology · 2026Article
- Analysis of GRK2 aggregation in the pathology of Alzheimer disease in animal models.Cell reports. Medicine · 2026Article
- The GPCR Connection: Linking Alzheimer's Disease and Glioblastoma.Journal of cellular and molecular medicine · 2026Review
- Unsupervised machine learning integrates genomic variants and EMR to unravel mechanisms of brain hemorrhage and epilepsy as early indicators of Alzheimer's in down syndrome.Alzheimer's research & therapy · 2025Article
- Functional Specificity of Astrocyte Subtypes in Alzheimer's Disease: Decoding Disease Mechanisms Through Network-based Analysis of Integrated Single-Nuclei Multi-Omic Data.Molecular neurobiology · 2025Article
- Circulating Biomarkers for the Early Diagnosis of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Gnb5 is a negative regulator of the BACE1-mediated Aβ generation and ameliorates cognitive deficits in a mouse model of Alzheimer's disease.PLoS biology · 2025Article
- Prediction of mild cognitive impairment using blood multi-omics data.Frontiers in genetics · 2025Article
- Article
- Dissecting the shared genetic architecture between Alzheimer's disease and frailty: a cross-trait meta-analyses of genome-wide association studies.Frontiers in genetics · 2024Article
- GPCR kinases generate an APH1A phosphorylation barcode to regulate amyloid-β generation.Cell reports · 2022Article
- Alzheimer's disease is an inherent, natural part of human brain aging: an integrated perspective.Free neuropathology · 2022Article
- Decoding Genetic Markers of Multiple Phenotypic Layers Through Biologically Constrained Genome-To-Phenome Bayesian Sparse Regression.Frontiers in molecular medicine · 2022Article
- Circulating extracellular vesicle-containing microRNAs reveal potential pathogenesis of Alzheimer's disease.Frontiers in cellular neuroscience · 2022Article
- NEU1-A Unique Therapeutic Target for Alzheimer's Disease.Frontiers in pharmacology · 2022Review
- Parkinson's Disease Dementia: Synergistic Effects of Alpha-Synuclein, Tau, Beta-Amyloid, and Iron.Frontiers in aging neuroscience · 2021Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
aimAlzheimer's disease (AD) is characterised by extracellular deposition of amyloid-β (Aβ) in amyloid plaques and intracellular aggregation and accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFTs). Although several kinases have been identified to contribute to the pathological phosphorylation of tau, kinase-targeted therapies for AD have not been successful in clinical trials. Critically, the kinases responsible for numerous identified tau phosphorylation sites remain unknown. G protein-coupled receptor (GPCR) kinases (GRKs) have recently been implicated in phosphorylation of non-GPCR substrates, for example, tubulin and α-synuclein, and in neurological disorders, including schizophrenia and Parkinson's disease. Accordingly, we investigated the involvement of GRKs in the pathophysiology of AD.
methodsWe performed a comprehensive immunohistochemical and biochemical analysis of the ubiquitously expressed GRKs, namely, GRK2, 3, 5 and 6, in postmortem human brain tissue of control subjects and AD patients.
resultsGRKs display unique cell-type-specific expression patterns in neurons, astrocytes and microglia. Levels of GRKs 2, 5 and 6 are specifically decreased in the CA1 region of the AD hippocampus. Biochemical evidence indicates that the GRKs differentially associate with total, soluble and insoluble pools of tau in the AD brain. Complementary immunohistochemical studies indicate that the GRKs differentially colocalise with total tau, phosphorylated tau and NFTs. Notably, GRKs 3 and 5 also colocalise with amyloid plaques.
conclusionThese studies establish a link between GRKs and the pathological phosphorylation and accumulation of tau and amyloid pathology in AD brains and suggest a novel role for these kinases in regulation of the pathological hallmarks of AD.
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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 Socratic graph.