ArticleBrain : a journal of neurology2021
Ageing promotes pathological alpha-synuclein propagation and autonomic dysfunction in wild-type rats.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 3 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 3 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- Experimental models of gut-first Parkinson's disease: A systematic review.Neurogastroenterology and motility · 2023Pooled it
- Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies.Frontiers in aging neuroscience · 2022Pooled it
- Impact of aging on animal models of Parkinson's disease.Frontiers in aging neuroscience · 2022Pooled it
- Brain-first and body-first subtypes of Lewy body disease.Nature reviews. Neurology · 2026Review
- Cutaneous alpha-synuclein deposition informs autonomic function in individuals with early-stage multiple system atrophy.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Article
- Duodenal α-Synuclein PFF Injection Induces Vagus-Related Gut-to-Brain Pathology in C57BL/6J and A53T Transgenic Mice.Brain sciences · 2026Article
- Age-dependent peripheral dissemination of α-synuclein seeds: mechanistic basis for blood-based early detection of Parkinson's disease.Acta neuropathologica communications · 2026Article
- Human and Mouse Alpha-Synuclein Fibrillation: Impact on h-FTAA Binding and Advancing Strain-Specific Biomarkers in PD Animal Models.International journal of molecular sciences · 2026Article
- Interpretable deep learning reveals spatiotemporal MRI features of brain aging that align with neurodegeneration.GeroScience · 2026Article
- Association Between Acupuncture's Neuroprotective Effects and Integrin Alpha 7.Medicina (Kaunas, Lithuania) · 2026Article
- Fluorescence Detection of Alpha-Synuclein Aggregates in the Gut Using a Peptide Probe.ACS chemical neuroscience · 2026Article
- Ten-Year Retrospective Study on the Diagnostic Value of Three-Site Skin Biopsy for Detecting pS129-α-Synuclein Biomarker: Cervical and Leg Dual-Site Biopsy as an Effective and Less Invasive Alternative.European journal of neurology · 2026Article
- Olfactory impairment and probable REM sleep behavior disorder in Parkinson's disease: clinical relevance to the single- and dual-hit hypotheses.Frontiers in aging neuroscience · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Selective amygdala subregional atrophy in Parkinson's disease: from subjective cognitive decline to mild cognitive impairment.Frontiers in aging neuroscience · 2026Article
- Aquaporin-4 mis-localization decreases glymphatic clearance of α-synuclein in an alpha-syntrophin knock out mouse model and promotes α-synuclein pathology and aggregate propagation.Brain communications · 2026Article
- Diet-gut microbiota-immune-brain interactions in aging: mechanistic pathways and clinical implications.Frontiers in molecular neuroscience · 2026Review
- Targeting Cdc42 improves motor phenotype in Parkinson's disease mice and reveals age-dependent susceptibility to α-synuclein.iScience · 2025Article
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- Acute Myocardial Infarction: Molecular Pathogenesis, Diagnosis, and Clinical Management.MedComm · 2025Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal aggregates of misfolded alpha-synuclein protein are found in the brain and periphery of patients with Parkinson's disease. Braak and colleagues have hypothesized that the initial formation of misfolded alpha-synuclein may start in the gut, and then spread to the brain via peripheral autonomic nerves hereby affecting several organs, including the heart and intestine. Age is considered the greatest risk factor for Parkinson's disease, but the effect of age on the formation of pathology and its propagation has not been studied in detail. We aimed to investigate whether propagation of alpha-synuclein pathology from the gut to the brain is more efficient in old versus young wild-type rats, upon gastrointestinal injection of aggregated alpha-synuclein. Our results demonstrate a robust age-dependent gut-to-brain and brain-to-gut spread of alpha-synuclein pathology along the sympathetic and parasympathetic nerves, resulting in age-dependent dysfunction of the heart and stomach, as observed in patients with Parkinson's disease. Moreover, alpha-synuclein pathology is more densely packed and resistant to enzymatic digestion in old rats, indicating an age-dependent maturation of alpha-synuclein aggregates. Our study is the first to provide a detailed investigation of alpha-synuclein pathology in several organs within one animal model, including the brain, skin, heart, intestine, spinal cord and autonomic ganglia. Taken together, our findings suggest that age is a crucial factor for alpha-synuclein aggregation and complete propagation to heart, stomach and skin, similar to patients. Given that age is the greatest risk factor for human Parkinson's disease, it seems likely that older experimental animals will yield the most relevant and reliable findings. These results have important implications for future research to optimize diagnostics and therapeutics in Parkinson's disease and other age-associated synucleinopathies. Increased emphasis should be placed on using aged animals in preclinical studies and to elucidate the nature of age-dependent interactions.
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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 OpenQuestion graph.