Topic: Brain proteins, microglia and lab models
Niemann-Pick type C1 disease (NPC1) is an autosomal recessive neurovisceral storage disease caused by the mutation of NPC1 gene, resulting in perturbed intracellular transport of unesterified cholesterol. In NPC1, early-onset tauopathy is a constant feature. In addition, in NPC1 patients with ApoE epsilon4 homozygosity, deposition of A beta occurs mimicking Alzheimer disease (AD). Since AD is frequently associated with neuronal expression of alpha-synuclein, we investigated phosphorylated alpha-synuclein (psyn) immunoreactivity in the brains of 12 NPC1 patients, ages at death ranging from 9 months to 55 years. Psyn immunoreactivity was demonstrated in the perikarya of storage neurons and oligodendroglia in 10 cases. The immunoreactivity appeared more intense in subjects who had the ApoE epsilon4 allele. Lewy bodies were found in the substantia nigra in 2 of these cases. The psyn immunoreactivity was most intense in the substantia nigra where tauopathy was most severe. Phosphorylated tau and alpha-synuclein frequently colocalized. This study first documents alpha-synucleinopathy in NPC1. This observation suggests that the defect in intracellular cholesterol trafficking in NPC1 may provoke aberrant phosphorylation of alpha-synuclein and tau, and that this phosphorylation is enhanced by the ApoE epsilon4 allele. Thus, elucidation of metabolic pathways in NPC1 could provide clues to common mechanisms associated with neurodegeneration.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Saito, Y., Suzuki, K., Hulette, C. M., & Murayama, S. (2004). Aberrant phosphorylation of alpha-synuclein in human Niemann-Pick type C1 disease. Journal of neuropathology and experimental neurology. https://doi.org/10.1093/jnen/63.4.323
Vancouver
Saito Y, Suzuki K, Hulette CM, Murayama S. Aberrant phosphorylation of alpha-synuclein in human Niemann-Pick type C1 disease. Journal of neuropathology and experimental neurology. 2004. doi:10.1093/jnen/63.4.323. PMID: 15099022.
BibTeX
@article{saito2004-15099022,
author = {Saito, Y. and Suzuki, K. and Hulette, C. M. and Murayama, S.},
title = {{Aberrant phosphorylation of alpha-synuclein in human Niemann-Pick type C1 disease}},
journal = {Journal of neuropathology and experimental neurology},
year = {2004},
doi = {10.1093/jnen/63.4.323},
pmid = {15099022},
url = {https://doi.org/10.1093/jnen/63.4.323}
}
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Key findings
- Since AD is frequently associated with neuronal expression of alpha-synuclein, we investigated phosphorylated alpha-synuclein (psyn) immunoreactivity in the brains of 12 NPC1 patients, ages at death ranging from 9 months to 55 years.
- Psyn immunoreactivity was demonstrated in the perikarya of storage neurons and oligodendroglia in 10 cases.
- This observation suggests that the defect in intracellular cholesterol trafficking in NPC1 may provoke aberrant phosphorylation of alpha-synuclein and tau, and that this phosphorylation is enhanced by the ApoE epsilon4 allele.
- Thus, elucidation of metabolic pathways in NPC1 could provide clues to common mechanisms associated with neurodegeneration.
Why it matters
In brain tissue from 12 patients with Niemann-Pick type C1 disease, abnormal phosphorylated alpha-synuclein was found in most cases and was more intense in those with the APOE ε4 allele. This is a small autopsy study of a different rare disease and does not test treatment for Alzheimer disease.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuropathology and experimental neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2004 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 97 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.0 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 2 / 6 | Cited 1.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Shigeo Murayama: h-index 83 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of North Carolina at Chapel Hill: institution h-index 1,674 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15099022) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 41 / 100 | — |
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