Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models
Computer-vision and machine-learning (ML) approaches are being developed to provide scalable, unbiased, and sensitive methods to assess mouse behavior. Here, we used the ML-based variational animal motion embedding (VAME) segmentation platform to assess spontaneous behavior in humanized App knockin and transgenic APP models of Alzheimer's disease (AD) and to test the role of AD-related neuroinflammation in these behavioral manifestations. We found marked alterations in spontaneous behavior in App<sup>NL-G-F</sup> and 5xFAD mice, including age-dependent changes in motif utilization, disorganized behavioral sequences, increased transitions, and randomness. Notably, blocking fibrinogen-microglia interactions in 5xFAD-Fgg<sup>γ390-396A</sup> mice largely prevented spontaneous behavioral alterations, indicating a key role for neuroinflammation. Thus, AD-related spontaneous behavioral alterations are prominent in knockin and transgenic models and sensitive to therapeutic interventions. VAME outcomes had higher specificity and sensitivity than conventional behavioral outcomes. We conclude that spontaneous behavior effectively captures age- and sex-dependent disease manifestations and treatment efficacy in AD models.
Authors
- Pranav Nambiar (ORCID: https://orcid.org/0000-0001-8154-8622)
- Jungpil Shin (ORCID: https://orcid.org/0000-0002-7476-2468)
- Katerina Akassoglou (ORCID: https://orcid.org/0000-0002-2632-1465)
- Takashi Saito (ORCID: https://orcid.org/0000-0002-9659-9251)
- Katie K. Ly
- Pavol Bauer
- Takaomi C. Saido (ORCID: https://orcid.org/0000-0003-1970-6903)
- Kevin Shen (ORCID: https://orcid.org/0000-0002-1773-038X)
- Reuben Thomas (ORCID: https://orcid.org/0000-0003-3176-7303)
- Andrew S. Mendiola (ORCID: https://orcid.org/0000-0002-2897-3299)
- Patrick Honma (ORCID: https://orcid.org/0000-0002-5349-0993)
- Zhaoqi Yan (ORCID: https://orcid.org/0000-0001-9326-2920)
- Catherine W. Cai (ORCID: https://orcid.org/0000-0003-1855-7950)
- Kevin Luxem (ORCID: https://orcid.org/0000-0001-9298-0314)
- Stefan Remy (ORCID: https://orcid.org/0000-0002-3386-1662)
- Yuechen Qiu
- Alexander R. Pico (ORCID: https://orcid.org/0000-0001-5706-2163)
- Jorge J. Palop (ORCID: https://orcid.org/0000-0001-6086-1070)
- Erik D. Roberson (ORCID: https://orcid.org/0000-0002-1810-9763)
- Stephanie R. Miller (ORCID: https://orcid.org/0000-0002-7350-3149)
- Mary Bullock
- N. Kaliss
- Kelli Lauderdale (ORCID: https://orcid.org/0000-0002-1943-7128)
- K Dakota Mallen
- Shreya C. Bangera (ORCID: https://orcid.org/0009-0001-9881-0559)
Institutions
- Gladstone Institutes (US)
- RIKEN Center for Brain Science (JP)
- German Center for Neurodegenerative Diseases (DE)
- University of Alabama at Birmingham (US)
- Nagoya City University (JP)
- Center for Behavioral Brain Sciences (DE)
- Leibniz Institute for Neurobiology (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-10-19
- DOI
- https://doi.org/10.1016/j.celrep.2024.114870
- Citations
- 16
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 5.22
Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health