Document Type
Article
Publication Date
8-1-2026
Original Citation
Oblak A,
Sasner M,
Carter GW,
Howell G,
Sukoff Rizzo S,
Leal K,
Territo P,
Lamb B.
The past, the present, and the future of preclinical mouse models for Alzheimer's disease and related dementias. Alzheimers Dement. 2026 Aug;22(8):e71741.
Keywords
JMG, Animals, Disease Models, Animal, Alzheimer Disease, Humans, Mice
JAX Source
Alzheimers Dement. 2026 Aug;22(8):e71741.
ISSN
1552-5279
PMID
42569823
DOI
https://doi.org/10.1002/alz.71741
Grant
MODEL-AD is supported through a grant from the National Institutes on Aging (U54AG054345)
Abstract
Over the past decade, the Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease (MODEL-AD) consortium has transformed preclinical Alzheimer's disease (AD) research by addressing critical limitations in traditional mouse models that failed to translate to human disease. By leveraging human genetic discoveries, MODEL-AD has developed > 70 genetically informed mouse models, standardized phenotyping pipelines, and an open-access data infrastructure aligned with late-onset AD biology. These models incorporate human risk variants, environmental factors, and aging to better capture disease complexity, including emerging recognition of mixed pathologies such as vascular contributions, Lewy body disease, and TDP-43 proteinopathy. Despite substantial progress, key challenges remain, including modeling multimorbidity, integrating aging, and improving translational predictability. Here, we outline a strategic roadmap spanning short-, intermediate-, and long-term approaches to refine disease modeling, enhance preclinical testing rigor, and support precision medicine. Continued investment in MODEL-AD will be essential to accelerate therapeutic discovery and establish a scalable framework for studying complex neurodegenerative diseases.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.