Proteomic identification of HNE-bound proteins in early Alzheimer disease: Insights into the role of lipid peroxidation in the progression of AD.

Authors: Reed, Tanea T  Pierce, William M  Markesbery, William R  Butterfield, D Allan 
Citation: Reed TT, etal., Brain Res. 2009 Jun 5;1274:66-76. doi: 10.1016/j.brainres.2009.04.009. Epub 2009 Apr 15.
Pubmed: (View Article at PubMed) PMID:19374891
DOI: Full-text: DOI:10.1016/j.brainres.2009.04.009

Early Alzheimer's disease (EAD) is the intermediary stage between mild cognitive impairment (MCI) and late-stage Alzheimer's disease (AD). The symptoms of EAD mirror the disease advancement between the two phases. Dementia, memory deficits, and cognitive decline are more pronounced as the disease progresses. Oxidative stress in brain is reported in MCI and AD, including lipid peroxidation indexed by protein-bound 4-hydroxy-2-nonenal (HNE). There are limited data regarding the proteomics analysis of brain from subjects with EAD and even less concerning the possible relationship of EAD HNE-modified brain proteins with HNE-modified proteins in MCI and AD. Proteomics was utilized to investigate excessively HNE-bound brain proteins in EAD compared to those in control. These new results provide potentially valuable insight into connecting HNE-bound brain proteins in EAD to those previously identified in MCI and AD, since EAD is a transitional stage between MCI and late-stage AD. In total, six proteins were found to be excessively covalently bound by HNE in EAD inferior parietal lobule (IPL) compared to age-related control brain. These proteins play roles in antioxidant defense (manganese superoxide dismutase), neuronal communication and neurite outgrowth (dihydropyriminidase-related protein 2), and energy metabolism (alpha-enolase, malate dehydrogenase, triosephosphate isomerase, and F1 ATPase, alpha subunit). This study shows that there is an overlap of brain proteins in EAD with previously identified oxidatively modified proteins in MCI and late-stage AD. The results are consistent with the hypothesis that oxidative stress, in particular lipid peroxidation, is an early event in the progression of AD, and is the first to identify in EAD identical brain proteins previously identified as HNE-modified in MCI and late-state AD.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 13703046
Created: 2018-07-30
Species: All species
Last Modified: 2018-07-30
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.