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      Is Alzheimer’s Also a Stem Cell Disease? – The Zebrafish Perspective

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          Abstract

          Alzheimer’s disease (AD) is the most common neurodegenerative disease and is the leading form of dementia. AD entails chronic inflammation, impaired synaptic integrity and reduced neurogenesis. The clinical and molecular onsets of the disease do not temporally overlap and the initiation phase of the cellular changes might start with a complex causativeness between chronic inflammation, reduced neural stem cell plasticity and neurogenesis. Although the immune and neuronal aspects in AD are well studied, the neural stem cell-related features are far less investigated. An intriguing question is, therefore, whether a stem cell can ever be made proliferative and neurogenic during the prevalent AD in the brain. Recent findings affirm this hypothesis and thus a plausible way to circumvent the AD phenotypes could be to mobilize the endogenous stem cells by enhancing their proliferative and neurogenic capacity as well as to provide the newborn neurons the potential to survive and integrate into the existing circuitry. To address these questions, zebrafish offers unprecedented information and tools, which can be effectively translated into mammalian experimental systems.

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          Most cited references100

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          Alzheimer's disease.

          Alzheimer's disease is the most common cause of dementia. Research advances have enabled detailed understanding of the molecular pathogenesis of the hallmarks of the disease--ie, plaques, composed of amyloid beta (Abeta), and tangles, composed of hyperphosphorylated tau. However, as our knowledge increases so does our appreciation for the pathogenic complexity of the disorder. Familial Alzheimer's disease is a very rare autosomal dominant disease with early onset, caused by mutations in the amyloid precursor protein and presenilin genes, both linked to Abeta metabolism. By contrast with familial disease, sporadic Alzheimer's disease is very common with more than 15 million people affected worldwide. The cause of the sporadic form of the disease is unknown, probably because the disease is heterogeneous, caused by ageing in concert with a complex interaction of both genetic and environmental risk factors. This seminar reviews the key aspects of the disease, including epidemiology, genetics, pathogenesis, diagnosis, and treatment, as well as recent developments and controversies.
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            Inflammation and Alzheimer's disease.

            Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid beta peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder.
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              Organoids as an in vitro model of human development and disease.

              The in vitro organoid model is a major technological breakthrough that has already been established as an essential tool in many basic biology and clinical applications. This near-physiological 3D model facilitates an accurate study of a range of in vivo biological processes including tissue renewal, stem cell/niche functions and tissue responses to drugs, mutation or damage. In this Review, we discuss the current achievements, challenges and potential applications of this technique.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                23 November 2018
                2018
                : 6
                : 159
                Affiliations
                [1] 1German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association , Dresden, Germany
                [2] 2Center for Regenerative Therapies Dresden, Cluster of Excellence, Technische Universität Dresden , Dresden, Germany
                Author notes

                Edited by: Eirini Trompouki, Max-Planck-Institut für Immunbiologie und Epigenetik, Germany

                Reviewed by: Steffen Scholpp, University of Exeter, United Kingdom; Felix Loosli, Karlsruher Institut für Technologie (KIT), Germany

                This article was submitted to Stem Cell Research, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2018.00159
                6265475
                30533414
                0fff9a11-0bb7-4712-9447-d57888bd58e5
                Copyright © 2018 Kizil and Bhattarai.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 September 2018
                : 06 November 2018
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 168, Pages: 10, Words: 0
                Funding
                Funded by: Helmholtz-Gemeinschaft 10.13039/501100001656
                Funded by: Deutsches Zentrum für Neurodegenerative Erkrankungen 10.13039/501100005224
                Funded by: Zentrum für Regenerative Therapien Dresden 10.13039/501100007491
                Funded by: Technische Universität Dresden 10.13039/501100002957
                Funded by: Deutsche Forschungsgemeinschaft 10.13039/501100001659
                Categories
                Cell and Developmental Biology
                Perspective

                zebrafish,alzheimer’s disease,neural stem/progenitor cells,regeneration,neurogenesis

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