Publication

Targeted Quantification of Detergent-Insoluble RNA-Binding Proteins in Human Brain Reveals Stage and Disease Specific Co-aggregation in Alzheimer's Disease

Downloadable Content

Persistent URL
Last modified
  • 05/14/2025
Type of Material
Authors
    Qi Guo, Emory UniversityEric Dammer, Emory UniversityMaotian Zhou, Emory UniversitySean R. Kundinger, Emory UniversityMarla Gearing, Emory UniversityJames Lah, Emory UniversityAllan Levey, Emory UniversityJoshua M. Shulman, Baylor College of MedicineNicholas Seyfried, Emory University
Language
  • English
Date
  • 2021-03-18
Publisher
  • Frontiers Media SA
Publication Version
Copyright Statement
  • © 2021 Guo, Dammer, Zhou, Kundinger, Gearing, Lah, Levey, Shulman and Seyfried.
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 14
Start Page
  • 623659
End Page
  • 623659
Grant/Funding Information
  • Support for this research was provided by funding from the National Institute on Aging (R01AG053960, R01AG061800, RF1AG057471, RF1AG057470, R01AG057339, and RF1AG062181), the Accelerating Medicine Partnership for AD (U01AG046161 and U01AG061357), and the Emory Alzheimer’s Disease Research Center (P30AG066511).
Supplemental Material (URL)
Abstract
  • Core spliceosome and related RNA-binding proteins aggregate in Alzheimer’s disease (AD) brain even in early asymptomatic stages (AsymAD) of disease. To assess the specificity of RNA-binding protein aggregation in AD, we developed a targeted mass spectrometry approach to quantify broad classes of RNA-binding proteins with other pathological proteins including tau and amyloid beta (Aβ) in detergent insoluble fractions from control, AsymAD, AD and Parkinson’s disease (PD) brain. Relative levels of specific insoluble RNA-binding proteins across different disease groups correlated with accumulation of Aβ and tau aggregates. RNA-binding proteins, including splicing factors with homology to the basic-acidic dipeptide repeats of U1-70K, preferentially aggregated in AsymAD and AD. In contrast, PD brain aggregates were relatively depleted of many RNA-binding proteins compared to AsymAD and AD groups. Correlation network analyses resolved 29 distinct modules of co-aggregating proteins including modules linked to spliceosome assembly, nuclear speckles and RNA splicing. Modules related to spliceosome assembly and nuclear speckles showed stage-specific enrichment of insoluble RBPs from AsymAD and AD brains, whereas the RNA splicing module was reduced specifically in PD. Collectively, this work identifies classes of RNA-binding proteins that distinctly co-aggregate in detergent-insoluble fractions across the specific neurodegenerative diseases we examined.
Author Notes
Keywords
Research Categories
  • Health Sciences, Pathology
  • Health Sciences, Medicine and Surgery
  • Chemistry, Biochemistry
  • Biology, Neuroscience

Tools

Relations

In Collection:

Items

Thumbnail Title File Description Date Uploaded Visibility Actions
file details Publication File - vv5r4.pdf Primary Content 2025-05-13 Public Download