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Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease
Published on: May 13, 2010
Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS
Robert W Mahley1, Karl H Weisgraber, Yadong Huang
1Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA. rmahley@gladstone.ucsf.edu
Journal of Lipid Research
|December 25, 2008
Summary
Apolipoprotein E (apoE) variants, particularly apoE4, contribute to cardiovascular, neurological, and infectious diseases due to distinct structural features. Future research aims to develop interventions targeting apoE4
Area of Science:
- Biochemistry and Molecular Biology
- Genetics and Disease Pathogenesis
- Immunology and Infectious Diseases
Background:
- Apolipoprotein E (apoE) plays crucial roles beyond lipid metabolism.
- Structural variations among apoE isoforms (apoE2, apoE3, apoE4) influence their function and disease association.
- ApoE4 is a significant genetic risk factor for Alzheimer's disease and other pathologies.
Purpose of the Study:
- To elucidate the structure-function relationships of apoE isoforms.
- To understand the detrimental effects of apoE4 in various diseases.
- To explore potential clinical interventions for apoE4-related conditions.
Main Methods:
- Structure/function studies of apolipoprotein E isoforms.
- Analysis of apoE's role in lipoprotein metabolism and receptor binding.
- Investigation of apoE's influence on cardiovascular, neurological, and infectious disease susceptibility.
Main Results:
- ApoE2 exhibits defective low-density lipoprotein (LDL) receptor binding due to altered receptor-binding region structure, explaining type III hyperlipoproteinemia.
- ApoE4 is strongly linked to Alzheimer's disease and other neuropathologies, exacerbated by genetic, metabolic, and environmental factors.
- ApoE4 influences susceptibility to parasitic, bacterial, and viral infections, notably accelerating HIV/AIDS progression and opportunistic infections in homozygotes.
Conclusions:
- Distinct structural features of apoE isoforms, especially apoE4, underlie their varied roles in disease.
- ApoE4's detrimental effects span cardiovascular, neurological, and infectious disease domains.
- Future clinical strategies will focus on modulating apoE4 structure or its mediated pathological processes.
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