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

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

doi:10.1016/j.neurobiolaging.2010.08.016

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 journal › Article › peer-review

73 Scopus citations

Abstract

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 language	English
Pages (from-to)	1034-1044
Number of pages	11
Journal	Neurobiology of Aging
Volume	33
Issue number	6
DOIs	https://doi.org/10.1016/j.neurobiolaging.2010.08.016
State	Published - 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.

Funding

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.

Funders	Funder number
National Institutes of Health (NIH)	5P01-AG05119
National Institute on Aging	P30AG028383

Keywords

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

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2010.08.016

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title = "Elevated 4-hydroxyhexenal in Alzheimer's disease (AD) progression",

abstract = "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.",

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author = "Bradley, {Melissa A.} and Shuling Xiong-Fister and Markesbery, {William R.} and Lovell, {Mark A.}",

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.",

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AU - Lovell, Mark A.

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AB - 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.

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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