Ketamine does not rescue plaque load or gap detection in the 5XFAD mouse model of Alzheimer's disease.
Frontiers in aging neuroscience January 1, 2025 Alexa L Wright, Aldis P Weible, Olivia B Estes et al. 1 citation
In a 5XFAD mouse model of Alzheimer's disease, ketamine—given either as a single acute injection or as chronic daily doses over 15 weeks—did not reduce amyloid plaque load or improve performance on an auditory gap detection task, an early behavioral biomarker of Alzheimer's in both mice and humans. Chronic ketamine increased startle responses in the 5XFAD mice, but this likely reflected effects on stress or habituation rather than a rescue of Alzheimer's-related deficits. Strong correlations between gap detection deficits and plaque accumulation in the auditory cortex and caudal pontine reticular nucleus confirmed the validity of gap detection as an early Alzheimer's biomarker. Ketamine did not alter these correlations, indicating no beneficial effect on network disruption or sensory-behavioral deficits in this model.