학술논문

Cross-species translation of the Morris maze for Alzheimer's disease
Document Type
Report
Source
Journal of Clinical Investigation. February 1, 2016, p779, 5 p.
Subject
Brain research
Labyrinths -- Usage
Alzheimer's disease -- Models
Brain mapping -- Research
Health care industry
Usage
Models
Research
Language
English
ISSN
0021-9738
Abstract
Analogous behavioral assays are needed across animal models and human patients to improve translational research. Here, we examined the extent to which performance in the Morris water maze--the most frequently used behavioral assay of spatial learning and memory in rodents--translates to humans. We designed a virtual version of the assay for human subjects that includes the visible-target training, hidden-target learning, and probe trials that are typically administered in the mouse version. We compared transgenic mice that express human amyloid precursor protein (hAPP) and patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) to evaluate the sensitivity of performance measures in detecting deficits. Patients performed normally during visible-target training, while hAPP mice showed procedural learning deficits. In hidden-target learning and probe trials, hAPP mice and MCI-AD patients showed similar deficits in learning and remembering the target location. In addition, we have provided recommendations for selecting performance measures and sample sizes to make these assays sensitive to learning and memory deficits in humans with MCI-AD and in mouse models. Together, our results demonstrate that with careful study design and analysis, the Morris maze is a sensitive assay for detecting ADrelevant impairments across species.
Introduction Alzheimer's disease (AD) is becoming more prevalent in aging populations worldwide, and there are no effective treatments (1). Mouse models that recapitulate some aspects of AD have been useful [...]