Synergistic reduction in interfacial flexibility of TREM2<sup>R47H</sup> and ApoE4 may underlie AD pathology
TREM2<sup>WT</sup> samples diverse CDR2 conformations, challenging prior assumptions that an "open" CDR2 state is solely pathogenic. ApoE2 promotes dynamic reconfiguration of TREM2-ApoE2 complexes, preserving TREM2<sup>WT</sup>'s flexibility. ApoE4's hinge forms a unique binding pocket that enhances TREM2 binding. The TREM2<sup>R47H</sup>-ApoE4 complex exhibits mutual rigidity, suppressing CDR2 and hinge flexibility.
Authors
- Kayla G. Sprenger (ORCID: https://orcid.org/0000-0002-7505-7920)
- Emma C Aldrich (ORCID: https://orcid.org/0000-0002-5729-4738)
- Emma E Lietzke (ORCID: https://orcid.org/0009-0005-5040-418X)
- Kimberley D. Bruce (ORCID: https://orcid.org/0000-0001-5656-1534)
- David Saeb
Institutions
- University of Colorado Boulder (US)
- University of Colorado Anschutz Medical Campus (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1002/alz.70120
- Citations
- 9
- Primary Topic
- Inflammation biomarkers and pathways
- Type
- article
- Field-Weighted Citation Impact
- 5.58
Funders
- Colorado State University
- National Institutes of Health
- University of Colorado Boulder
- National Institute on Aging