Amyloid precursor protein regulates differentiation of human neural stem cells

    Authors

    Y. D. Kwak; C. L. Brannen; T. Qu; H. M. Kim; X. Dong; P. Soba; A. Majumdar; A. Kaplan; K. Beyreuther;K. Sugaya

    Comments

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    Abbreviated Journal Title

    Stem Cells Dev.

    Keywords

    ADULT SUBVENTRICULAR ZONE; ALZHEIMERS-DISEASE; BINDING PROTEIN; HUMAN; BRAIN; BETA; MICE; GENE; MIGRATION; APOPTOSIS; APP; Cell & Tissue Engineering; Hematology; Medicine, Research &; Experimental; Transplantation

    Abstract

    Although amyloid beta(A beta) deposition has been a hallmark of Alzheimer's disease (AD), the absence of a phenotype in the beta amyloid precursor protein (APP) knockout mouse, tends to detract our attention away from the physiological functions of APP. Although much attention has been focused on the neurotoxicity of A beta, many studies suggest the involvement of APP in neuroplasticity. We found that secreted amyloid precursor protein ( sAPP) increased the differentiation of human neural stem cells (hNSCs) in vitro, while an antibody-recognizing APP dose-dependently inhibited these activities. With a high dose of sAPP treatment or wild-type APP gene transfection, hNSCs were differentiated into astrocytes rather than neurons. In vivo, hNSCs transplanted into APP-transgenic mouse brain exhibited glial differentiation rather than neural differentiation. Our results suggest that APP regulates neural stem cell biology in the adult brain, and that altered APP metabolism in Down syndrome or AD may have implications for the pathophysiology of these diseases.

    Journal Title

    Stem Cells and Development

    Volume

    15

    Issue/Number

    3

    Publication Date

    1-1-2006

    Document Type

    Article

    Language

    English

    First Page

    381

    Last Page

    389

    WOS Identifier

    WOS:000239118100009

    ISSN

    1547-3287

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