title: Cross-species translation of the Morris maze for Alzheimer's disease.
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 AD-relevant impairments across species.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Possin
authors.forename: Pascal E
authors.initials: PE
authors.lastname: Sanchez
authors.forename: Clifford
authors.initials: C
authors.lastname: Anderson-Bergman
authors.forename: Roland
authors.initials: R
authors.lastname: Fernandez
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Kerchner
authors.forename: Erica T
authors.initials: ET
authors.lastname: Johnson
authors.forename: Allyson
authors.initials: A
authors.lastname: Davis
authors.forename: Iris
authors.initials: I
authors.lastname: Lo
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Bott
authors.forename: Thomas
authors.initials: T
authors.lastname: Kiely
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Fenesy
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.forename: Steven
authors.initials: S
authors.lastname: Finkbeiner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D013045:Species Specificity
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor