Untold New Beginnings: Adult Hippocampal Neurogenesis and Alzheimer’s Disease

Issue title: Alzheimer’s Disease: New Beginnings

Guest editors: G. Perry, J. Avila, P.I. Moreira, A.A. Sorensen and M. Tabaton

Article type: Review Article

Authors: Teixeira, Catia M.^{a; 1} | Pallas-Bazarra, Noemí^{b; c; 1} | Bolós, Marta^{b; c; 1} | Terreros-Roncal, Julia^{b; c} | Ávila, Jesús^{b; c} | Llorens-Martín, María^{b; c; d; *}

Affiliations: [a] Emotional Brain Institute, Nathan Kline Institute, New York, NY, USA | [b] Department of Molecular Neuropathology, Centro de Biología Molecular “Severo Ochoa”, CBMSO, CSIC-UAM, Madrid, Spain | [c] Center for Networked Biomedical Research on neurodegenerative diseases (CIBERNED), Madrid, Spain | [d] Department of Molecular Biology, Faculty of Sciences, Universidad Autónoma de Madrid, Madrid, Spain

Correspondence: [*] Correspondence to: María Llorens-Martín, Centro de Biología Molecular “Severo Ochoa”, Universidad Autónoma de Madrid (campus de Cantoblanco), c/Nicolás Cabrera 1, 28049, Madrid, Spain. Tel.: +34 911964592; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Neurogenesis occurs in a limited number of brain regions during adulthood. Of these, the hippocampus has attracted great interest due to its involvement in memory processing. Moreover, both the hippocampus and the main area that innervates this structure, namely the entorhinal cortex, show remarkable atrophy in patients with Alzheimer’s disease (AD). Adult hippocampal neurogenesis is a process that continuously gives rise to newborn granule neurons in the dentate gyrus. These cells coexist with developmentally generated granule neurons in this structure, and both cooperative and competition phenomena regulate the communication between these two types of cells. Importantly, it has been revealed that GSK-3β and tau proteins, which are two of the main players driving AD pathology, are cornerstones of adult hippocampal neurogenesis regulation. We have shown that alterations either promoting or impeding the actions of these two proteins have detrimental effects on the structural plasticity of granule neurons. Of note, these impairments occur both under basal conditions and in response to detrimental and neuroprotective stimuli. Thus, in order to achieve the full effectiveness of future therapies for AD, we propose that attention be turned toward identifying the pathological and physiological actions of the proteins involved in the pathogenesis of this condition.

Keywords: Adult hippocampal neurogenesis, Alzheimer’s disease, granule neuron, GSK-3β, morphology, neuroprotection, tau

DOI: 10.3233/JAD-179918

Journal: Journal of Alzheimer's Disease, vol. 64, no. s1, pp. S497-S505, 2018