Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C-terminal fragment of APP in primary cortical neurons

Sachin Patil, Lufang Sheng, Alexis Masserang, Christina Chan

    Research output: Research - peer-reviewArticle

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    Abstract

    High-fat diet is a significant risk factor for the development of Alzheimer's disease (AD). In addition, the AD brain is characterized by elevated levels of fatty acids as compared to that of healthy controls. Despite this, it is unclear how elevated levels of fatty acids are related to the pathogenesis of AD. The present study examines the role of saturated fatty acid, palmitic acid (PA), in causing BACE1 upregulation and consequent amyloidogenic processing of β-amyloid precursor protein (APP), one of the main characteristic signatures of AD pathology. Here, primary rat cortical neurons and astrocytes were treated with pathological concentration of PA. There was no change in the BACE1 levels in the rat cortical neurons treated directly with PA as compared to controls. The conditioned medium from PA-treated astrocytes, however, caused BACE1 upregulation in the cortical neurons. Moreover, there was a consequent increase in the cleavage of APP leading to the accumulation of the C-terminal fragment of APP (C99) in the cortical neurons. Co-treatment of neurons with 1,3-dimethyl urea (DMU), an antioxidant, decreased PA-induced upregulation in the levels of BACE1 and C99. The present results establish an important role of saturated fatty acids in AD-associated amyloidogenesis through astroglia-mediated oxidative stress.

    LanguageEnglish (US)
    Pages55-59
    Number of pages5
    JournalNeuroscience Letters
    Volume406
    Issue number1-2
    DOIs
    StatePublished - Oct 2 2006

    Profile

    Palmitic Acid
    Amyloid beta-Protein Precursor
    Astrocytes
    Alzheimer Disease
    Up-Regulation
    Neurons
    Fatty Acids
    Amyloid beta-Peptides
    High Fat Diet
    Conditioned Culture Medium
    Urea
    Oxidative Stress
    Antioxidants
    Pathology
    Brain

    Keywords

    • Alzheimer's disease
    • BACE1
    • Oxidative stress
    • Palmitic acid
    • Saturated fatty acids

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C-terminal fragment of APP in primary cortical neurons. / Patil, Sachin; Sheng, Lufang; Masserang, Alexis; Chan, Christina.

    In: Neuroscience Letters, Vol. 406, No. 1-2, 02.10.2006, p. 55-59.

    Research output: Research - peer-reviewArticle

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