To Determine if Adult Neurogenesis is Impaired in Alzheimer’s Disease Model

Abstract

Background and purpose: Neurogenesis is the process of the renewal of generated in the dentate gyrus (DG) in the hippocampus which occurs continuously throughout life. These cells can develop to be mature neurons and integrated into thepre-exitingneuronalnetwork. Thenewneuronsplayanimportantroletolearningandmemory.Itisbelieved that the mutations in the β-amyloid precursor protein (APP) lead to Amyloid beta fragment accumulation which causes a decrease in the neurogenesis process and thus leads to cognitive impairment in Alzheimer’s disease patients. The aim of this work is to test the effect of APP mutation on neurogenesis using a model mouse in which human amyloid precursor protein mutations knocked in which lead to accumulation of Aβ to induce cognitive impairment. Experimental approach Real time Polymerase chain reaction was performed using hippocampus and cortex tissues to measure the doublecortin (DCX) gene expression as a marker of immature neurons. POMC-GFP mice were used to image the live tissue to detect the number of immature neurons by using the Two- photon microscopy. Morphology analysis was carried out by using sholl analysis to detect the number of the intersections of dendrites. Immunohistochemistry was performed to detect doublecortin- positive cells with confocal microscopy. Key results APP mutations did not affected the DCX expression in the hippocampus tissue. Surprisingly, DCX was expressed in cortex tissue and showed a significant reduction in the HET and KI mice. The difference in the number of POMC-GFP neurons was not significant nor was the difference in the number of intersections in the sholl analysis. DCX immunostaining showed a reduction in the number of neurons in KI animal though this experiment was not completed. Overall, these human APP (Swedish and Iberian) mutations did not lead to neurogenesis reduction in the age range used in this work.