Cross-species translation of the Morris maze for Alzheimer's disease

The Journal of Clinical Investigation
Katherine L PossinSteven Finkbeiner

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 caref...Continue Reading

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Citations

Jan 20, 2016·The Journal of Clinical Investigation·Kerin K HigaMark A Geyer
Jun 2, 2016·Nature Communications·V BeglopoulosR G M Morris
Feb 26, 2019·Current Protocols in Pharmacology·Kevin Mullane, Michael Williams
Oct 23, 2019·Behavior Research Methods·Sean ComminsConor Thornberry
Aug 2, 2017·Canadian Journal of Physiology and Pharmacology·Mauro CeccantiMarco Fiore
Jan 31, 2020·Frontiers in Neurology·Hayo A BreinbauerPaul H Delano
Sep 25, 2018·Frontiers in Behavioral Neuroscience·Elísabet Bello-ArroyoMaría Victoria Gómez-Gaviro
Dec 8, 2020·Frontiers in Behavioral Neuroscience·Tavor Ben-ZeevEitan Okun
Nov 17, 2020·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Helen C BarronCassandra Sampaio-Baptista
Apr 11, 2021·Reviews in the Neurosciences·Conor ThornberrySean Commins
Sep 14, 2021·Journal of Neuroscience Research·Yifat Glikmann-JohnstonJulie C Stout

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Methods Mentioned

BETA
transgenic

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