ArticleScientific reports2023
Detection, visualization and quantification of protein complexes in human Alzheimer's disease brains using proximity ligation assay.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Disease-specific tau polymorphs are associated with unique protein networks across proteinopathies.The EMBO journal · 2026Article
- Antibody-oligonucleotide conjugates for spatial proteomics: principles, applications, and challenges.Acta biochimica et biophysica Sinica · 2025Article
- Proximity Ligation Assay: From a Foundational Principle to a Versatile Platform for Molecular and Translational Research.Biomolecules · 2025Review
- IQGAP2 regulates blood-brain barrier immune dynamics.iScience · 2025Article
- Advancement in human neuroimaging based on proximity ligation assay in brain disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- E-cadherin interacts with EGFR resulting in hyper-activation of ERK in multiple models of breast cancer.Oncogene · 2024Article
- Article
- IQGAP2 regulates blood-brain barrier immune dynamics.bioRxiv : the preprint server for biology · 2024Article
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13 authors at 3 institutions in 3 countries.
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Abstract
Examination of healthy and diseased human brain is essential to translational neuroscience. Protein-protein interactions play a pivotal role in physiological and pathological processes, but their detection is difficult, especially in aged and fixed human brain tissue. We used the in-situ proximity ligation assay (PLA) to broaden the range of molecular interactions assessable in-situ in the human neuropathology. We adapted fluorescent in-situ PLA to detect ubiquitin-modified proteins in human brains with Alzheimer's disease (AD), including approaches for the management of autofluorescence and quantification using a high-content image analysis system. We confirmed that phosphorylated microtubule-associated protein tau (Serine202, Threonine205) aggregates were modified by ubiquitin and that phospho-tau-ubiquitin complexes were increased in hippocampal and frontal cortex regions in AD compared to non-AD brains. Overall, we refined PLA for use in human neuropathology, which has revealed a profound change in the distribution of ubiquitin in AD brain and its association with characteristic tau pathologies.
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Registered trials
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