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: Contribution to journalArticle

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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: Contribution to journalArticle

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