Acrolein is increased in Alzheimer's disease brain and is toxic to primary hippocampal cultures

Mark A. Lovell, Chengsong Xie, William R. Markesbery

Research output: Contribution to journalArticlepeer-review

401 Scopus citations

Abstract

Accumulating evidence implicates oxidative stress in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE), F2-isoprostanes, and F4-neuroprostanes are present in the brain in AD. Acrolein, an α,β-unsaturated aldehydic product of lipid peroxidation, is approximately 100 times more reactive than HNE and recently was demonstrated in neurofibrillary tangles in the brain in AD. In three brain regions of 10 AD patients compared with 8 age-matched control subjects, we found increased mean extractable acrolein, with the increases reaching statistical significance in the amygdala and hippocampus/parahippocampal gyrus. In hippocampal neuron cultures, acrolein was neurotoxic in a time- and concentration-dependent manner and more toxic than HNE at 5 μM concentrations of each. Acrolein exposure led to a significant concentration-dependent increase in intracellular calcium concentrations. Collectively, these data show that acrolein is increased in the brain in AD and demonstrate neurotoxicity mechanisms that might be important in the pathogenesis of neuron degeneration in AD.

Original languageEnglish
Pages (from-to)187-194
Number of pages8
JournalNeurobiology of Aging
Volume22
Issue number2
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
Funding for this work was provided by NIH Grants 5-P01-AG05119, and 5-P50-AG05144, and by a grant from the Abercrombie Foundation. The authors thank Paula Thomason for editorial and Jane Meara for technical assistance in manuscript preparation, and Cecil Runyons for demographic data. We also thank Dr. Robert Hadley and Hema Gursahani for assistance with quantification of intracellular calcium.

Keywords

  • Alzheimer's disease
  • Brain
  • Free radicals
  • Lipid peroxidation
  • Neuronal cultures
  • Neurotoxin

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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