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Author Notes:

E-mail Address : cmhales@emory.edu E-mail Address : nseyfri@emory.edu E-mail Address : edammer@emory.edu E-mail Address : hyi@emory.edu E-mail Address : mgearin@emory.edu E-mail Address : alevey@emory.edu E-mail Address : jlah@emory.edu

CMH, NTS, EBD, AIL, and JJL. conceived and supervised the project. HY conducted electron microscopy. MG, EJM and JCT provided human samples. CMH performed all immunohistochemistry.

EBD performed proteomic analysis. CMH, NTS, EBD, AIL, and JJL all assisted in writing and editing the paper. EJM edited the manuscript. All authors read and approved the final manuscript.

We are grateful for pathological specimens provided by MG, JCT and Thomas Montine M.D, Ph.D.

The authors declare they have no competing interests


Research Funding:

This research project was supported in part by the Robert P. Apkarian Integrated Electron Microscopy Core of Emory University.

Clinical Research Training Fellowship from the American Brain Foundation (CMH).

Emory Alzheimer’s Disease Research Center-NIA-AG025688 (AIL), NIAP01AG14449 (JJL, EJM), Emory Neuroscience NINDS Core Facility-P30NS055077, University of Washington ADRC-NIA-P50-AG05136 and an Alzheimer’s Association New Investigator Research Award (NIRG-12-242297) to NTS.

This work was supported in part by the NIA intramural Research Program of the National Institutes of Health.


  • Spliceosome
  • snRNP
  • Alzheimer’s disease
  • Down syndrome
  • U1-70k
  • SmD
  • Presenilin
  • Amyloid precursor protein

U1 small nuclear ribonucleoproteins (snRNPs) aggregate in Alzheimer’s disease due to autosomal dominant genetic mutations and trisomy 21

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Journal Title:

Molecular Neurodegeneration


Volume 9, Number 15


Type of Work:

Article | Final Publisher PDF


Background We recently identified U1 small nuclear ribonucleoprotein (snRNP) tangle-like aggregates and RNA splicing abnormalities in sporadic Alzheimer’s disease (AD). However little is known about snRNP biology in early onset AD due to autosomal dominant genetic mutations or trisomy 21 in Down syndrome. Therefore we investigated snRNP biochemical and pathologic features in these disorders. Findings We performed quantitative proteomics and immunohistochemistry in postmortem brain from genetic AD cases. Electron microscopy was used to characterize ultrastructural features of pathologic aggregates. U1-70k and other snRNPs were biochemically enriched in the insoluble fraction of human brain from subjects with presenilin 1 (PS1) mutations. Aggregates of U1 snRNP-immunoreactivity formed cytoplasmic tangle-like structures in cortex of AD subjects with PS1 and amyloid precursor protein (APP) mutations as well as trisomy 21. Ultrastructural analysis with electron microscopy in an APP mutation case demonstrated snRNP immunogold labeling of paired helical filaments (PHF). Conclusions These studies identify U1 snRNP pathologic changes in brain of early onset genetic forms of AD. Since dominant genetic mutations and trisomy 21 result in dysfunctional amyloid processing, the findings suggest that aberrant β-amyloid processing may influence U1 snRNP aggregate formation.

Copyright information:

© 2014 Hales et al.; licensee BioMed Central Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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