Selective Long Term Memory impairment in transgenic McGill-R-Thy1-APP rat model of Alzheimer´s Disease

SALAS D; CUELLO C; HABIF M; CERCATO M; KORNISIUK E; FILIPPIN F; COLETTIS N; JERUSALINSKY D

Montreal

Congreso; 2019 ISN ASN Meeting; 2019

International Society for Neurochemistry y American Society for Neurochemistry

Memory impairment in early Alzheimer Disease (AD) is hypothesised to rely on the initial increase in soluble Ab-oligomers, potent neurotoxins altering synaptic plasticity.McGill-R-Thy1-APP Wistar-transgenic (Tg) rats, bearing human Amyloid Precursor Protein with Swedish and Indiana mutations of familial AD, offer a singular opportunity for testing learning and memory abilities at AD onset. Homozygous Tg rats show cognition deficits at 3 months; human Ab accumulates intra-neuronally from first postnatal week and develops extracellular amyloid pathology by 6-9 months. Hemizygous Tg (He) show a more subtle phenotype and do not develop extracellular plaques even at 20 months. 13 month old He rats and their wild type litter-mates (WT) were left to freely explore an open field (OF) for 5 min and tested 24 hr later (long-term-memory, LTM); bi-dimensional exploration was quantified, being significantly lower in test than in training for both groups.Rats were then trained in a two object recognition task (OR); both WT and He discriminated new vs. known object 1 hr later (shortterm-memory, STM), while He rats did not show LTM.They were then trained in an inhibitory avoidance (IA) to a mild foot-shock task. Latencies to go from an enlightened to a dark compartment where they get the shock, were recorded. Test latencies 24 hr later, were significantly higher than training latencies for WT, while remained unchanged for He.Therefore, unlike WT, He evidenced deficits in memory formation for object discrimination and for an associative memory involving aversive and spatial components.