Elevated 4-hydroxyhexenal in Alzheimer's disease (AD) progression

Melissa A. Bradley, Shuling Xiong-Fister, William R. Markesbery, Mark A. Lovell

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


Multiple studies have demonstrated elevations of α, β-unsaturated aldehydes including 4-hydroxynonenal (HNE) and acrolein, in vulnerable regions of mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), and late stage Alzheimer's disease (LAD) brain. However, there has been limited study of a third member, 4-hydroxyhexenal (HHE), a diffusible lipid peroxidation product of the ω-3 polyunstataturated fatty acids (PUFAs). In the present study levels of extractable and protein-bound HHE were quantified in the hippocampus/parahippocampal gyrus (HPG), superior and middle temporal gyri (SMTG), and cerebellum (CER) of MCI, PCAD, LAD, and normal control (NC) subjects. Levels of extractable and protein-bound HHE were increased in multiple regions in the progression of Alzheimer's disease (AD). Extractable HHE was significantly elevated in the hippocampus/parahippocampal gyrus (HPG) of PCAD and LAD subjects and protein-bound HHE was significantly higher in MCI, PCAD, and LAD HPG. A time- and concentration-dependent decrease in survival and a concentration-dependent decrease in glucose uptake were observed in primary cortical cultures treated with HHE. Together these data support a role for lipid peroxidation in the progression of Alzheimer's disease.

Original languageEnglish
Pages (from-to)1034-1044
Number of pages11
JournalNeurobiology of Aging
Issue number6
StatePublished - Jun 2012

Bibliographical note

Funding Information:
This research was supported by NIH grants 5P01-AG05119 and P30-AG028383 . The authors thank Ms. Sonya Anderson for subject demographic data, Ms. Paula Thomason for editorial assistance, the UK-ADC Neuropathology Core for histopathological data, Paul Murphy and the UK Amyloid Core for Aβ measurements, and Dr. Bert C. Lynn of the UK Mass Spectrometry Facility for MALDI mass spectrometry.


  • 4-Hydroxyhexenal
  • Alzheimer's disease (AD)
  • Lipid peroxidation
  • Mild cognitive impairment (MCI)
  • Neurodegenerative diseases
  • Preclinical Alzheimer's disease (PCAD)

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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