From genes to cognition: Octodon degus , an animal model for AD translational research

DEACON, ROBERT; ANGIONE, CLAUDIO; MUGNAINI, MATIAS; VANDERKLISH, PETER; COGRAM, PATRICIA; SAMPIERI, GUIDO; KROPFF, EMILIO

ALZHEIMERS & DEMENTIA

ELSEVIER SCIENCE INC

Año: 2020 vol. 16

1552-5260

Octodon degus (O. degus), a long-lived rodent, provides us with a uniqueopportunity to search for molecular pathways that are associated with enhancedlongevity in mammals. This rodent from Chile spontaneously develops an analog ofsporadic AD at behavioral and neurobiological levels. It is a diurnal rodent that makeswide use of spatial memory to find and hide food. This cognitive ability is thought to berooted in what is commonly known as the GPS of the mammalian brain, a collection ofstructures centred around the hippocampus and neighbouring cortical areas. A fractionof the aged O. degus population not only exhibits amyloid-beta oligomers, tau hyper-phosphorylation, neurofibrillary tangle formation, cell death and cognitive decline butalso several other conditions comorbid t o AD like diabetes mellitus type 2, macular andretinal degeneration and atherosclerosis. we here present the first multidis-ciplinary study including i) Recording 69 CA1 principal cells while O. degus exploreda 1 m wide square environment, finding that O. degus exhibited extreme place cellbehaviour. ii)We performed a genome-wide association study in O. degus and reportthe identification of SNVs in genes associated with AD (APP, BACE1, MAPT, Psen1and Psen2, grn and SORL1. iii) Some of the variants identified in AD associated genesshowed significant association with behavioural performance in Hardy-Weinberg equilibrium.