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Publication : Marked Mild Cognitive Deficits in Humanized Mouse Model of Alzheimer's-Type Tau Pathology.

First Author  Cho JD Year  2021
Journal  Front Behav Neurosci Volume  15
Pages  634157 PubMed ID  34093145
Mgi Jnum  J:314500 Mgi Id  MGI:6813599
Doi  10.3389/fnbeh.2021.634157 Citation  Cho JD, et al. (2021) Marked Mild Cognitive Deficits in Humanized Mouse Model of Alzheimer's-Type Tau Pathology. Front Behav Neurosci 15:634157
abstractText  Hyperphosphorylation and the subsequent aggregation of tau protein into neurofibrillary tangles (NFTs) are well-established neuropathological hallmarks of Alzheimer's disease (AD) and associated tauopathies. To further examine the impact and progression of human tau pathology in neurodegenerative contexts, the humanized tau (htau) mouse model was originally created. Despite AD-like tau pathological features recapitulated in the htau mouse model, robustness of behavioral phenotypes has not been fully established. With the ultimate goal of evaluating the htau mouse model as a candidate for testing AD therapeutics, we set out to verify, in-house, the presence of robust, replicable cognitive deficits in the htau mice. The present study shows behavioral data collected from a carefully curated battery of learning and memory tests. Here we report a significant short-term spatial memory deficit in aged htau mice, representing a novel finding in this model. However, we did not find salient impairments in long-term learning and memory previously reported in this mouse model. Here, we attempted to understand the discrepancies in the literature by highlighting the necessity of scrutinizing key procedural differences across studies. Reported cognitive deficits in the htau model may depend on task difficulty and other procedural details. While the htau mouse remains a unique and valuable animal model for replicating late onset AD-like human tau pathology, its cognitive deficits are modest under standard testing conditions. The overarching message is that before using any AD mouse model to evaluate treatment efficacies, it is imperative to first characterize and verify the presence of behavioral deficits in-house.
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