Aggregates of Small Nuclear Ribonucleic Acids ( snRNAs ) in A lzheimer's Disease
Open accessAbstract
We recently discovered that protein components of the ribonucleic acid ( RNA ) spliceosome form cytoplasmic aggregates in A lzheimer's disease ( AD ) brain, resulting in widespread changes in RNA splicing. However, the involvement of small nuclear RNAs ( snRNAs ), also key components of the spliceosome complex, in the pathology of AD remains unknown. Using immunohistochemical staining of post‐mortem human brain and spinal cord, we identified cytoplasmic tangle‐shaped aggregates of snRNA in both sporadic and familial AD cases but not in aged controls or other neurodegenerative disorders. Immunofluorescence using antibodies reactive with the 2,2,7‐trimethylguanosine cap of snRNAs and transmission electron microscopy demonstrated snRNA localization with tau and paired helical filaments, the main component of neurofibrillary tangles. Quantitative real‐time polymerase chain reaction ( PCR ) showed U 1 snRNA accumulation in the insoluble fraction of AD brains whereas other U snRNAs were not enriched. In combination with our previous results, these findings demonstrate that aggregates of U 1 snRNA and U 1 small nuclear ribonucleoproteins represent a new pathological hallmark of AD .
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Many U1 snRNPs colocalize with neurofibrillary tangles and paired helical filaments in AD brain.
“Interestingly, our previous studies demonstrated that many of the U1 snRNPs colocalize with neurofibrillary tangles and paired helical filaments in AD brain [24, 32–34], and that accumulation of insoluble snRNPs correlates strongly with both amyloid and Tau pathology [32–37].”
From Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease (2018) · cites this paper as [33]
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- Authors
- Hales, C. M., Dammer, E. B., Diner, I., Yi, H., Seyfried, N. T., Gearing, M., Glass, J. D., Montine, T. J., Levey, A. I., & Lah, J. J.
- Affiliations
- Emory University (US)
- University of Washington (US)
- ORCID
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 2014-04-14
- Volume
- 24
- Issue
- 4
- Pages
- 344-351
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC4096308
- OpenAlex
- W1909655902
- Cited by
- 89
- References
- 26
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 8 · 2022: 9 · 2021: 11 · 2020: 6 · 2019: 8 · 2018: 11 · 2017: 7 · 2016: 6 · 2015: 6 · 2014: 3
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG025688, NIAP01AG1449, AG05136, AG038259)
- National Institute of Neurological Disorders and Stroke (P30NS055077)
- Alzheimer's Association (NIRG-12-242297)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, small nuclear RNA, U1 snRNA, RNA splicing, spliceosome, neurofibrillary tangles, tau protein, paired helical filaments, U1 snRNP
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cytoplasm, Female, Fluorescent Antibody Technique, Humans, Male, Middle Aged, RNA, Small Nuclear, Spinal Cord, Neurofibrillary Tangles, tau Proteins, Tauopathies, Microscopy, Electron, Transmission, Real-Time Polymerase Chain Reaction
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