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

Sachin Patil, Christina Chan

Research output: Contribution to journalArticle

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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

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: Contribution to journalArticle

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