Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons

Sachin Patil, Christina Chan

    Research output: Research - peer-reviewArticle

    • 61 Citations

    Abstract

    Epidemiological studies suggest that high fat diets significantly increase the risk of Alzheimer's disease (AD). In addition, the AD brain is characterized by high fatty acid content compared to that of healthy subjects. Nevertheless, the basic mechanism relating elevated fatty acids and the pathogenesis of AD remains unclear. The present study examines the role of fatty acids in causing hyperphosphorylation of the tau protein, one of the characteristic signatures of AD pathology. Hyperphosphorylation of tau disrupts the cell cytoskeleton and leads to neuronal degeneration. Here, primary rat cortical neurons and astrocytes were treated with saturated free fatty acids (FFAs), palmitic and stearic acids. There was no change in the levels of phosphorylated tau in rat cortical neurons treated directly with these FFAs. The conditioned media from FFA-treated astrocytes, however, caused hyperphosphorylation of tau in the cortical neurons at AD-specific phospho-epitopes. Co-treatment of neurons with N-acetyl cysteine, an antioxidant, reduced FFA-induced hyperphosphorylation of tau. The present results establish a central role of FFAs in causing hyperphosphorylation of tau through astroglia-mediated oxidative stress.

    LanguageEnglish (US)
    Pages288-293
    Number of pages6
    JournalNeuroscience Letters
    Volume384
    Issue number3
    DOIs
    StatePublished - Aug 26 2005

    Profile

    Stearic Acids
    Nonesterified Fatty Acids
    Alzheimer Disease
    Neurons
    Fatty Acids
    Astrocytes
    tau Proteins
    High Fat Diet
    Conditioned Culture Medium
    Cytoskeleton
    Cysteine
    Epidemiologic Studies
    Epitopes
    Healthy Volunteers
    Oxidative Stress
    Antioxidants
    Pathology
    Brain
    Therapeutics

    Keywords

    • Alzheimer's disease
    • Oxidative stress
    • Primary cortical neurons
    • Saturated fatty acids
    • Tau hyperphosphorylation

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons. / Patil, Sachin; Chan, Christina.

    In: Neuroscience Letters, Vol. 384, No. 3, 26.08.2005, p. 288-293.

    Research output: Research - peer-reviewArticle

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