ArticleAlzheimer's research & therapy2014
Evaluating the relationship between amyloid-β and α-synuclein phosphorylated at Ser129 in dementia with Lewy bodies and Parkinson's disease.
Article in Alzheimer's research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed.
- Benefits of Gut Microbiota Reconstitution by Beta 1,3-1,6 Glucans in Subjects with Autism Spectrum Disorder and Other Neurodegenerative Diseases.Journal of Alzheimer's disease : JAD · 2023Trial
- Neuropathological correlates of imaging in dementia with Lewy bodies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Meprin-β levels are increased in the brain and the cerebrospinal fluid of Alzheimer's disease patients.Alzheimer's research & therapy · 2026Article
- Selective reduction of ADAM10 in brain and cerebrospinal fluid of Alzheimer's disease patients.Alzheimer's research & therapy · 2026Article
- α-Synuclein expression is required for somatodendritic dopamine release and immediate early gene induction.Science advances · 2026Article
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- Toward common treatment strategies: convergent proteinopathies and mitochondrial dysfunction in Alzheimer's and Parkinson's diseases.Frontiers in neuroscience · 2026Review
- Lewy body dementia: exploring biomarkers and pathogenic interactions of amyloid β, tau, and α-synuclein.Molecular neurodegeneration · 2025Review
- Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy.NPJ Parkinson's disease · 2025Article
- Aβ42 biomarker linked to insula, striatum, thalamus and claustrum in dementia with Lewy bodies.GeroScience · 2025Article
- Novel tools to quantify total, phospho-Ser129 and aggregated alpha-synuclein in the mouse brain.NPJ Parkinson's disease · 2024Article
- Structural Variations of Prions and Prion-like Proteins Associated with Neurodegeneration.Current issues in molecular biology · 2024Review
- Prevalence of Concomitant Pathologies in Parkinson's Disease: Implications for Prognosis, Diagnosis, and Insights into Common Pathogenic Mechanisms.Journal of Parkinson's disease · 2024Review
- The central role of the Thalamus in psychosis, lessons from neurodegenerative diseases and psychedelics.Translational psychiatry · 2023Review
- Article
- Complement receptor 3-mediated neurotoxic glial activation contributes to rotenone-induced cognitive decline in mice.Ecotoxicology and environmental safety · 2023Article
- A Precision Medicine Approach to Dementia Care: Syndrome, Etiology, and Copathology.Practical neurology (Fort Washington, Pa.) · 2023Article
- Protein Interactome of Amyloid-β as a Therapeutic Target.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Serum neurofilament light chain levels in patients with cognitive deficits and movement disorders: comparison of cerebrospinal and serum neurofilament light chain levels with other biomarkers.Frontiers in human neuroscience · 2023Article
- Plasma biomarkers inclusive of α-synuclein/amyloid-beta40 ratio strongly correlate with Mini-Mental State Examination score in Parkinson's disease and predict cognitive impairment.Journal of neurology · 2022Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
introductionLewy body and Alzheimer-type pathologies often co-exist. Several studies suggest a synergistic relationship between amyloid-β (Aβ) and α-synuclein (α-syn) accumulation. We have explored the relationship between Aβ accumulation and the phosphorylation of α-syn at serine-129 (pSer129 α-syn), in post-mortem human brain tissue and in SH-SY5Y neuroblastoma cells transfected to overexpress human α-syn.
methodsWe measured levels of Aβ40, Aβ42, α-syn and pSer129 α-syn by sandwich enzyme-linked immunosorbent assay, in soluble and insoluble fractions of midfrontal, cingulate and parahippocampal cortex and thalamus, from cases of Parkinson's disease (PD) with (PDD; n = 12) and without dementia (PDND; n = 23), dementia with Lewy bodies (DLB; n = 10) and age-matched controls (n = 17). We also examined the relationship of these measurements to cognitive decline, as measured by time-to-dementia and the mini-mental state examination (MMSE) score in the PD patients, and to Braak tangle stage.
resultsIn most brain regions, the concentration of insoluble pSer129 α-syn correlated positively, and soluble pSer129 α-syn negatively, with the levels of soluble and insoluble Aβ. Insoluble pSer129 α-syn also correlated positively with Braak stage. In most regions, the levels of insoluble and soluble Aβ and the proportion of insoluble α-syn that was phosphorylated at Ser129 were significantly higher in the PD and DLB groups than the controls, and higher in the PDD and DLB groups than the PDND brains. In PD, the MMSE score correlated negatively with the level of insoluble pSer129 α-syn. Exposure of SH-SY5Y cells to aggregated Aβ42 significantly increased the proportion of α-syn that was phosphorylated at Ser129 (aggregated Aβ40 exposure had a smaller, non-significant effect).
conclusionsTogether, these data show that the concentration of pSer129 α-syn in brain tissue homogenates is directly related to the level of Aβ and Braak tangle stage, and predicts cognitive status in Lewy body diseases.
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