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U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer's disease
Bai B, Hales CM, Chen PC, Gozal Y, Dammer EB, Fritz JJ, Wang X, Xia Q et al.. Proceedings of the National Academy of Sciences of the United States of America, 2013-09-10
Topic: Amyloid, tau and blood-test diagnosis
Deposition of insoluble protein aggregates is a hallmark of neurodegenerative diseases. The universal presence of β-amyloid and tau in Alzheimer's disease (AD) has facilitated advancement of the amyloid cascade and tau hypotheses that have dominated AD pathogenesis research and therapeutic development. However, the underlying etiology of the disease remains to be fully elucidated. Here we report a comprehensive study of the human brain-insoluble proteome in AD by mass spectrometry. We identify 4,216 proteins, among which 36 proteins accumulate in the disease, including U1-70K and other U1 small nuclear ribonucleoprotein (U1 snRNP) spliceosome components. Similar accumulations in mild cognitive impairment cases indicate that spliceosome changes occur in early stages of AD. Multiple U1 snRNP subunits form cytoplasmic tangle-like structures in AD but not in other examined neurodegenerative disorders, including Parkinson disease and frontotemporal lobar degeneration. Comparison of RNA from AD and control brains reveals dysregulated RNA processing with accumulation of unspliced RNA species in AD, including myc box-dependent-interacting protein 1, clusterin, and presenilin-1. U1-70K knockdown or antisense oligonucleotide inhibition of U1 snRNP increases the protein level of amyloid precursor protein. Thus, our results demonstrate unique U1 snRNP pathology and implicate abnormal RNA splicing in AD pathogenesis.
Key findings
- Similar accumulations in mild cognitive impairment cases indicate that spliceosome changes occur in early stages of AD.
- Thus, our results demonstrate unique U1 snRNP pathology and implicate abnormal RNA splicing in AD pathogenesis.
Why it matters
In brain tissue, U1 snRNP spliceosome components accumulated in Alzheimer's disease and were already present in mild cognitive impairment, with unspliced RNA species building up. This identifies a possible disease process but does not test any treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 52/100
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 (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 2013 — within 20 year(s) of the newest study here |
| 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 | 6 / 7 | Cited 333 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.2 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 12.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 74 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Junmin Peng: h-index 98 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24023061) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1073/pnas.1310249110
- PubMed: 24023061
- Original source →
- Free full text: Proceedings of the National Academy of Sciences →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Bai, B., Hales, C. M., Chen, P. C., Gozal, Y., Dammer, E. B., Fritz, J. J., et al. (2013). U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1310249110
Vancouver
Bai B, Hales CM, Chen PC, Gozal Y, Dammer EB, Fritz JJ, et al. U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America. 2013. doi:10.1073/pnas.1310249110. PMID: 24023061.
BibTeX
@article{bai2013-24023061,
author = {Bai, B. and Hales, C. M. and Chen, P. C. and Gozal, Y. and Dammer, E. B. and Fritz, J. J. and Wang, X. and Xia, Q. and others},
title = {{U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer's disease}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2013},
doi = {10.1073/pnas.1310249110},
pmid = {24023061},
url = {https://doi.org/10.1073/pnas.1310249110}
}
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