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- Title
Detection, visualization and quantification of protein complexes in human Alzheimer's disease brains using proximity ligation assay.
- Authors
Romero-Fernandez, Wilber; Carvajal-Tapia, Cristian; Prusky, Alex; Katdare, Ketaki A.; Wang, Emmeline; Shostak, Alena; Ventura-Antunes, Lissa; Harmsen, Hannah J.; Lippmann, Ethan S.; Fuxe, Kjell; MacGurn, Jason A.; Borroto-Escuela, Dasiel O.; Schrag, Matthew S.
- 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.
- Subjects
ALZHEIMER'S disease; BRAIN diseases; TAU proteins; FRONTAL lobe; MICROTUBULE-associated proteins; TUBULINS; IMAGE analysis
- Publication
Scientific Reports, 2023, Vol 13, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-023-38000-4