TREM2 risk variants and associated endophenotypes in alzheimer’s disease
This study shows that while carriers of TREM2 risk variants cannot be distinguished based on clinical presentation at baseline compared to non-carriers, they do exhibit a faster global cognitive decline. Variant-specific analyses indicate that especially R47H and T96K carriers drive this association. These results highlight the importance of considering variant-specific effects for understanding the role of TREM2 biology in AD. The rich phenotype information can inform clinical stage drug development.
Authors
- Lisa Vermunt (ORCID: https://orcid.org/0000-0001-7420-6384)
- Marc Hulsman (ORCID: https://orcid.org/0000-0002-9889-3606)
- Rik Ossenkoppele (ORCID: https://orcid.org/0000-0003-1584-7477)
- Betty Marije Tijms (ORCID: https://orcid.org/0000-0002-2612-1797)
- Wiesje M. van der Flier (ORCID: https://orcid.org/0000-0001-8766-6224)
- Emma M. Coomans (ORCID: https://orcid.org/0000-0002-4289-9101)
- Elsmarieke van de Giessen
- Henne Holstege (ORCID: https://orcid.org/0000-0002-7688-3087)
- Vikram Venkatraghavan (ORCID: https://orcid.org/0000-0001-9759-0462)
- Frederik Barkhof (ORCID: https://orcid.org/0000-0003-3543-3706)
- Alida A. Gouw (ORCID: https://orcid.org/0000-0003-1481-3881)
- Janna I.R. Dijkstra (ORCID: https://orcid.org/0000-0003-3673-2513)
- Christa M. de Geus (ORCID: https://orcid.org/0000-0002-7996-056X)
- Sietske A.M. Sikkes (ORCID: https://orcid.org/0000-0002-0161-3656)
- Charlotte Elisabeth Teunissen (ORCID: https://orcid.org/0000-0002-4061-0837)
- Everard G.B. Vijverberg (ORCID: https://orcid.org/0000-0003-3879-884X)
- Willem de Haan (ORCID: https://orcid.org/0000-0002-0527-9667)
- Yolande A.L. Pijnenburg (ORCID: https://orcid.org/0000-0003-2464-1905)
- Sven J. van der Lee
- Georgii Ozhegov
Institutions
- Lund University (SE)
- Amsterdam Neuroscience (NL)
- GGD Amsterdam (NL)
- National Hospital for Neurology and Neurosurgery (GB)
- Amsterdam University Medical Centers (NL)
- University College London (GB)
- Vrije Universiteit Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Delft University of Technology (NL)
Publication Details
- Journal
- Alzheimer s Research & Therapy
- Published
- 2025-03-06
- DOI
- https://doi.org/10.1186/s13195-025-01700-2
- Citations
- 12
- Primary Topic
- Inflammation biomarkers and pathways
- Type
- article
- Field-Weighted Citation Impact
- 9.57