Apolipoprotein E modulates Alzheimer’s Aβ(1–42)-induced oxidative damage to synaptosomes in an allele-specific manner

Lauderback, Christopher M.; Kański, Jarosław; Hackett, Janna M.; Maeda, Noboyo; Kindy, Mark S.; Butterfield, D. Allan

doi:10.1016/s0006-8993(01)03228-0

Cited by 125 publications

(75 citation statements)

References 59 publications

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“…APOE*4 may stress the brain by causing synaptic disruption. 32 In response, the brain may attempt to restore neuronal integrity by increasing the production of tau or AS. Alternatively, the degradation process may decrease, resulting in protein accumulation and aggregation.…”

Section: Discussionmentioning

confidence: 99%

Genetic association between the APOE * 4 allele and Lewy bodies in Alzheimer disease

Tsuang¹,

Wilson²,

López³

et al. 2005

Neurology

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Objective: To explore the association between APOE*4 and pathologically confirmed cases of the Lewy body (LB) variant of Alzheimer disease (AD). Methods: With use of α-synuclein (AS) immunohistochemistry, LBs were detected in 74 of 131 (56.5%) of the AD + LB cases; the remaining 57 cases (43.5%) did not have LBs. Results: There were no differences in gender or age between Caucasian subjects with AD + LB or AD alone or control subjects. The APOE*4 allele frequency was highest in the AD + LB group (47.3%; 95% CI = 37.8 to 57.0%), intermediate in the AD-alone group (35.1%; 95% CI = 25.3 to 46.3%), and lowest in the control group (14.2%; 95% CI = 10.5 to 18.9%). With use of logistic regression analysis, the odds of having AD + LB vs AD alone were 2.1-fold (95% CI = 1.0 to 4.5, p = 0.055) greater in persons with an APOE*4 allele than in those without

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Section: Discussionmentioning

confidence: 99%

Genetic association between the APOE * 4 allele and Lewy bodies in Alzheimer disease

Tsuang¹,

Wilson²,

López³

et al. 2005

Neurology

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“…Similarly, in postmortem AD brain, Tamaoka et al [14] measured thiobarbituric-acid-reactive substances, an index of lipid peroxidation, and obtained the highest values in brains with ApoE Â4/Â4. Moreover, measurement of specific markers of oxidation in synaptosomes isolated from mice that express one of the human ApoE alleles indicated that Aß-induced increases in these markers were always greatest in Â4 synaptosomes as compared to Â3 and Â2 synaptosomes [15]. In light of these observations, our finding that the presence of the mutant H63D allele in ApoE Â4 homozygotes promotes an earlier onset of AD is consistent with the hypothesis that increased iron-mediated oxidative stress may result from the H63D mutation, and that this oxidative damage is accelerated as a result of the lowest antioxidant activity of the ApoE Â4 allele.…”

Section: Discussionmentioning

confidence: 99%

Interaction of the H63D Mutation in the Hemochromatosis Gene with the Apolipoprotein E Epsilon 4 Allele Modulates Age at Onset of Alzheimer’s Disease

Combarros¹,

García-Román

Fontalba

et al. 2003

Dement Geriatr Cogn Disord

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The H63D mutation in the hemochromatosis gene (HFE) has recently been considered as a risk factor in Alzheimer`s disease (AD) with advancing age at onset of the disease, independently of the apolipoprotein E (ApoE) Ε4 allele effect. We examined the distribution of the H63D mutation and ApoE genotypes as a function of age at AD onset in 328 patients with sporadic AD. Our data show that the mutant H63D allele potentially interacts with the ApoE Ε4 allele to significantly reduce age at onset of AD compared to ApoE Ε4 carriers alone, but has no effect on age at onset in ApoE Ε4 non-carriers.

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“…55 ␤-actin was found to be significantly oxidized in synaptosomes treated with A␤(1-42) consistent with its reported oxidation in AD brain. 56 Protein oxidation has been shown to lead to protein conformational changes 57,58 and loss of protein function. 7,59 Based on this notion, oxidation and subsequent loss of function of the proteins identified in this study 51 would lead to excitotoxicity, disruption of the synapse, and impairment of energy metabolism, all of which are implicated in AD.…”

Section: A␤(1-42) In Synaptosomesmentioning

confidence: 99%

Redox proteomics in some age-related neurodegenerative disorders or models thereof

et al. 2006

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Summary:Neurodegenerative diseases cause memory loss and cognitive impairment. Results from basic and clinical scientific research suggest a complex network of mechanisms involved in the process of neurodegeneration. Progress in treatment of such disorders requires researchers to better understand the functions of proteins involved in neurodegenerative diseases, to characterize their role in pathogenic disease mechanisms, and to explore their roles in the diagnosis, treatment, and prevention of neurodegenerative diseases. A variety of conditions of neurodegenerative diseases often lead to post-translational modifications of proteins, including oxidation and nitration, which might be involved in the pathogenesis of neurodegenerative diseases. Redox proteomics, a subset of proteomics, has made possible the identification of specifically oxidized proteins in neurodegenerative disorders, providing insight into a multitude of pathways that govern behavior and cognition and the response of the nervous system to injury and disease. Proteomic analyses are particularly suitable to elucidate post-translational modifications, expression levels, and protein-protein interactions of thousands of proteins at a time. Complementing the valuable information generated through the integrative knowledge of protein expression and function should enable the development of more efficient diagnostic tools and therapeutic modalities. Here we review redox proteomic studies of some neurodegenerative diseases.

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Apolipoprotein E modulates Alzheimer’s Aβ(1–42)-induced oxidative damage to synaptosomes in an allele-specific manner

Cited by 125 publications

References 59 publications

Genetic association between the APOE * 4 allele and Lewy bodies in Alzheimer disease

Genetic association between the APOE * 4 allele and Lewy bodies in Alzheimer disease

Interaction of the H63D Mutation in the Hemochromatosis Gene with the Apolipoprotein E Epsilon 4 Allele Modulates Age at Onset of Alzheimer’s Disease

Redox proteomics in some age-related neurodegenerative disorders or models thereof

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