Neurogenesis in the adult brain takes place in two neurogenic niches: the ventricular-subventricular zone (V-SVZ) and the subgranular zone. After differentiation, neural precursor cells (neuroblasts) have to move to an adequate position, a process known as neuronal migration. Some studies show that in Alzheimer's disease, the adult neurogenesis is impaired. Our main aim was to investigate some proteins involved both in the physiopathology of Alzheimer's disease and in the neuronal migration process using the APP/PS1 Alzheimer's mouse model. Progenitor migrating cells are accumulated in the V-SVZ of the APP/PS1 mice. Furthermore, we find an increase of Cdh1 levels and a decrease of Cdk5/p35 and cyclin B1, indicating that these cells have an alteration of the cell cycle, which triggers a senescence state. We find less cells in the rostral migratory stream and less mature neurons in the olfactory bulbs from APP/PS1 mice, leading to an impaired odour discriminatory ability compared with WT mice. Alzheimer's disease mice present a deficit in cell migration from V-SVZ due to a senescent phenotype. Therefore, these results can contribute to a new approach of Alzheimer's based on senolytic compounds or pro-neurogenic factors.

2nd Faculty of Medicine Charles University Prague Czech Republic

CIBERFES Institute of Health Research INCLIVA Valencia Spain

Departament of Biotecnology Universitat Politècnica de València Valencia Spain

Department of Psychobiology Faculty of Psycology University of Valencia Valencia Spain

Freshage Research Group Department of Physiology Faculty of Medicine University of Valencia Valencia Spain

Institute of Experimental Medicine Czech Academy of Sciences Prague Czech Republic

Laboratory of Comparative Neurobiology Instituto Cavanilles de Biodiversidad Y Biologia Evolutiva University of Valencia CIBERNED Paterna Valencia Spain

Neuronal and Tissue Regeneration Laboratory Centro de Investigación Príncipe Felipe Valencia Spain

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