Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease.
Hung-Kai Chen,Zhong-Sheng Ji,Sara E. Dodson,Rene D. Miranda,Charles Rosenblum,Ian J. Reynolds,Stephen B. Freedman,Karl H. Weisgraber,Yadong Huang,Robert W. Mahley +9 more
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TLDR
The results suggest that pharmacological intervention with small molecules that disrupt apoE4 domain interaction is a potential therapeutic approach for apOE4-carrying AD subjects.About:
This article is published in Journal of Biological Chemistry.The article was published on 2011-02-18 and is currently open access. It has received 161 citations till now. The article focuses on the topics: Respiratory function & Mitochondrion.read more
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Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
TL;DR: Increasing evidence suggests that the effect of APOE*ε4 on AD risk is exerted through inhibition of amyloid-β (Aβ) clearance and promotion of Aβ aggregation, although the relevance of this observation to AD pathogenesis requires further investigation.
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The Alzheimer's disease mitochondrial cascade hypothesis: progress and perspectives.
TL;DR: The mitochondrial cascade hypothesis unequivocally states in sporadic, late-onset AD, mitochondrial function affects amyloid precursor protein (APP) expression, APP processing, or beta amyloids (Aβ) accumulation and argues if an amyloidal cascade truly exists, mitochondria function triggers it.
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Mitochondria and Mitochondrial Cascades in Alzheimer's Disease.
TL;DR: This review considers studies and data that inform this area of AD research and suggests mitochondrial dysfunction exists independent of Aβ, potentially lies upstream of A β deposition, and suggest a primary mitochondrial cascade hypothesis that assumes mitochondrial pathology hierarchically supersedes Aβ pathology.
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Age, APOE and sex: Triad of risk of Alzheimer's disease.
TL;DR: The data indicate complex interactions between age, APOE genotype and gender that belies a one size fits all approach and argues for a precision medicine approach that integrates across the three main risk factors for Alzheimer's disease.
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Apolipoprotein E in Alzheimer's Disease: An Update
Jin-Tai Yu,Lan Tan,John Hardy +2 more
TL;DR: Emerging data suggest that APOE contributes to AD pathogenesis through both amyloid-β (Aβ)-dependent and Aβ-independent pathways and the utility of APOE genotyping in AD diagnosis, risk assessment, prevention, and treatment response is suggested.
References
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Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
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Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases
Michael T. Lin,M. Flint Beal +1 more
TL;DR: Treatments targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria hold great promise in ageing-related neurodegenerative diseases.
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Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Warren J. Strittmatter,Ann M. Saunders,Donald E. Schmechel,Margaret A. Pericak-Vance,Jan J. Enghild,Guy S. Salvesen,Allen D. Roses +6 more
TL;DR: It is demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon 4) and late-onset familial Alzheimer disease.
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Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.
TL;DR: Apolipoprotein E is a plasma protein that serves as a ligand for low density lipoprotein receptors and, through its interaction with these receptors, participates in the transport of cholesterol and other lipids among various cells of the body.
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A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine
TL;DR: The mitochondria provide a direct link between the authors' environment and their genes and the mtDNA variants that permitted their forbears to energetically adapt to their ancestral homes are influencing their health today.