ArticleBrain : a journal of neurology2022
Prion-like α-synuclein pathology in the brain of infants with Krabbe disease.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Sphingolipidoses: expanding the spectrum of α-synucleinopathies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- α-Synuclein in Lewy Body Diseases: Progress, Remaining Challenges and Future Perspectives.Expert reviews in molecular medicine · 2026Review
- Testing an inverse link between limbic alpha-synucleinopathy and myelin markers in mice and humans.NPJ Parkinson's disease · 2026Article
- Where do PDD and DLB SYNdromes fit in neuronal alpha-SYNuclein biological frameworks?Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases.Progress in neurobiology · 2025Review
- Leveraging bioorthogonal conjugation for alpha synuclein fibril surveillance.bioRxiv : the preprint server for biology · 2025Article
- Current strategies in the management of dementia with lewy bodies and future directions based on disease pathophysiology.Molecular neurodegeneration · 2025Review
- How do different cell populations orchestrate myelin regeneration?Biochemical Society transactions · 2025Review
- Broken Balance: Emerging Cross-Talk Between Proteostasis and Lipostasis in Neurodegenerative Diseases.Cells · 2025Review
- Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological disease.Immunity · 2025Article
- Biomarker-Based Approach to α-Synucleinopathies: Lessons from Neuropathology.Movement disorders : official journal of the Movement Disorder Society · 2024Article
- Role of Lipids in the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2024Review
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Distinct sets of lysosomal genes define synucleinopathy and tauopathy.BMB reports · 2023Article
- Review
- Impaired Autophagy in Krabbe Disease: The Role of BCL2 and Beclin-1 Phosphorylation.International journal of molecular sciences · 2023Article
- Globoid Cell Leukodystrophy (Krabbe Disease): An Update.ImmunoTargets and therapy · 2023Review
- Article
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Authors and funding
17 authors at 8 institutions in 5 countries.
Funding
Abstract
Krabbe disease is an infantile neurodegenerative disorder resulting from pathogenic variants in the GALC gene that causes accumulation of the toxic sphingolipid psychosine. GALC variants are also associated with Lewy body diseases, an umbrella term for age-associated neurodegenerative diseases in which the protein α-synuclein aggregates into Lewy bodies. To explore whether α-synuclein in Krabbe disease has pathological similarities to that in Lewy body disease, we performed an observational post-mortem study of Krabbe disease brain tissue (n = 4) compared to infant controls (n = 4) and identified widespread accumulations of α-synuclein. To determine whether α-synuclein in Krabbe disease brain displayed disease-associated pathogenic properties we evaluated its seeding capacity using the real-time quaking-induced conversion assay in two cases for which frozen tissue was available and strikingly identified aggregation into fibrils similar to those observed in Lewy body disease, confirming the prion-like capacity of Krabbe disease-derived α-synuclein. These observations constitute the first report of prion-like α-synuclein in the brain tissue of infants and challenge the putative view that α-synuclein pathology is merely an age-associated phenomenon, instead suggesting it results from alterations to biological pathways, such as sphingolipid metabolism. Our findings have important implications for understanding the mechanisms underlying Lewy body formation in Lewy body disease.
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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.