Early behavioral abnormalities are independent of extracellular ABeta accumulation in a new transgenic rat model of Alzheimer's disease

GALEANO, PABLO; MARTINO ADAMI, PAMELA V; BLANCO CALVO, EDUARDO; LOGICA TORNATORE, TAMARA; CAPANI, FRANCISCO; CASTAÑO, EDUARDO M; MORELLI, LAURA

Oviedo

Congreso; 15° Congreso Nacional de la Sociedad Española de Neurociencia; 2013

Sociedad Española de Neurociencia

Contradictory results have been obtained between the amount of amyloid deposition and the degree of cognitive decline in Alzheimer´s disease (AD). On the contrary, intraneuronal ABeta accumulation has been linked to the mild cognitive impairment that precedes AD onset. Leon et al. (2010) have developed a new AD transgenic rat model that express the human amyloid precursor protein (ABetaPP) with the Swedish and Indiana mutations (McGill-R-Thy1-APP). The heterozygous transgenic rat has the advantage of not developing amyloid plaque deposition during its entire lifespan. Objective. To assess locomotor activity, emotional reactivity and cognitive performance at a young age in an AD transgenic rat model that only accumulates Abeta intracellularly. Materials and methods. 3-month-old heterozygous male transgenic rats (+/-tg, n=10) and their male wild-type littermates (wt, n=9) were evaluated in a behavioral test battery that included: Elevated Plus Maze (EPM), Open Field (OF), Novel Object Recognition Test, Y-maze spontaneous alternation test and a spatial learning and reference memory protocol in the Morris Water Maze (MWM). After behavioral tests were completed, the intraneuronal ABeta accumulation was assessed by immunohistochemistry, using the antibody McSA1 which is specific for the human ABeta peptide. Results. In EPM and OF tests, +/-tg rats displayed higher levels of anxiety than their wt littermates. In the MWM, +/-tg rats showed spatial reference memory impairment during the probe trial. In contrast, episodic-like memory, working memory and spatial learning were preserved. Immunohistochemistry results confirmed that amyloid beta accumulated intraneuronally in the hippocampus and cerebral cortex. Extracellular ABeta accumulation was not observed. Conclusions. Our results indicate that this heterozygous line exhibits emotional and cognitive alterations as early as 3 months of age. Since rats display a more complex behavioral repertoire than mice, this transgenic model could be interesting for testing therapeutic interventions for behavioral alterations that take place during preclinical stages of AD.