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@ARTICLE{Miller:272860,
author = {Miller, Stephanie R and Luxem, Kevin and Lauderdale, Kelli
and Nambiar, Pranav and Honma, Patrick S and Ly, Katie K and
Bangera, Shreya and Bullock, Mary and Shin, Jia and Kaliss,
Nick and Qiu, Yuechen and Cai, Catherine and Shen, Kevin and
Mallen, K Dakota and Yan, Zhaoqi and Mendiola, Andrew S and
Saito, Takashi and Saido, Takaomi C and Pico, Alexander R
and Thomas, Reuben and Roberson, Erik D and Akassoglou,
Katerina and Bauer, Pavol and Remy, Stefan and Palop, Jorge
J},
title = {{M}achine learning reveals prominent spontaneous behavioral
changes and treatment efficacy in humanized and transgenic
{A}lzheimer's disease models.},
journal = {Cell reports},
volume = {43},
number = {11},
issn = {2211-1247},
address = {[New York, NY]},
publisher = {Elsevier},
reportid = {DZNE-2024-01278},
pages = {114870},
year = {2024},
abstract = {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 AppNL-G-F and 5xFAD mice,
including age-dependent changes in motif utilization,
disorganized behavioral sequences, increased transitions,
and randomness. Notably, blocking fibrinogen-microglia
interactions in 5xFAD-Fggγ390-396A 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.},
keywords = {Alzheimer Disease: pathology / Alzheimer Disease: genetics
/ Animals / Machine Learning / Humans / Mice, Transgenic /
Disease Models, Animal / Mice / Behavior, Animal / Male /
Female / Treatment Outcome / Amyloid beta-Protein Precursor:
genetics / Amyloid beta-Protein Precursor: metabolism /
Mice, Inbred C57BL / App-KI (Other) / CP: Neuroscience
(Other) / DeepLabCut (Other) / Keypoint-MoSeq (Other) /
amyloid (Other) / behavioral segmentation (Other) /
cognition (Other) / naturalistic behavior (Other) / open
field (Other) / pose estimation (Other) / preclinical
(Other)},
cin = {AG Remy},
ddc = {610},
cid = {I:(DE-2719)1013006},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39427315},
doi = {10.1016/j.celrep.2024.114870},
url = {https://pub.dzne.de/record/272860},
}