ArticleNPJ Parkinson's disease2024
MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity.
Article in NPJ Parkinson's disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- ONE microscopy.Nature protocols · 2026Review
- Seeing Invisible Oligomers: Rethinking α-Synuclein Pathology Through Proximity Ligation Assay.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation.Cell reports · 2026Article
- Ultrastructural diversity and subcellular organization of nigral Lewy pathology in Parkinson's disease.Nature communications · 2026Article
- Lewy Bodies Are Not Associated With Neuronal or Synaptic Loss in Dementia With Lewy Bodies.Neuropathology and applied neurobiology · 2026Article
- von Willebrand Factor fibers formed at pathological high shear provide a scaffold for α-synuclein binding and aggregation.Scientific reports · 2026Article
- Focused Ultrasound for the Treatment of Circuit and Molecular Pathology in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- Higher-molecular-weight a-synuclein oligomers are increased in the brain cytosol of patients with dementia with Lewy bodies.NPJ Parkinson's disease · 2026Article
- Distinct AQP4 Alterations in Movement Disorders with Primary Synucleinopathy.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- Imbalanced mitochondrial dynamics in human PD and α-synuclein mouse brains.Neurobiology of disease · 2025Article
- Differential pathological dynamics triggered by distinct Parkinson patient-derived α-synuclein extracts in nonhuman primates.Science advances · 2025Article
- Abundant non-inclusion α-synuclein pathology in Lewy body-negative LRRK2-mutant cases.Acta neuropathologica · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
α-Synuclein proximity ligation assay (PLA) has proved a sensitive technique for detection of non-Lewy body α-synuclein aggregate pathology. Here, we describe the MJF-14 PLA, a new PLA towards aggregated α-synuclein with unprecedented specificity, using the aggregate-selective α-synuclein antibody MJFR-14-6-4-2 (hereafter MJF-14). Signal in the assay correlates with α-synuclein aggregation in cell culture and human neurons, induced by α-synuclein overexpression or pre-formed fibrils. Co-labelling of MJF-14 PLA and pS129-α-synuclein immunofluorescence in post-mortem cases of dementia with Lewy bodies shows that while the MJF-14 PLA reveals extensive non-inclusion pathology, it is not sensitive towards pS129-α-synuclein-positive Lewy bodies. In Parkinson's disease brain, direct comparison of PLA and immunohistochemistry with the MJF-14 antibody shows widespread α-synuclein pathology preceding the formation of conventional Lewy pathology. In conclusion, we introduce an improved α-synuclein aggregate PLA to uncover abundant non-inclusion pathology, which deserves future validation with brain bank resources and in different synucleinopathies.
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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 Socratic graph.