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Aging-Related and Gender Specific Albumin Misfolding in Alzheimer’s Disease
Aging-related protein misfolding and aggregation may play critical roles in the pathogenesis of numerous diseases. In the brain, extracellular aggregated amyloid-β (Aβ) is closely related to the death of neurons in individuals with Alzheimer’s disease (AD). Albumin-Aβ binding is important in prevent...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175925/ https://www.ncbi.nlm.nih.gov/pubmed/32328565 http://dx.doi.org/10.3233/ADR-200168 |
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author | Tsao, Francis H.C. Barnes, Jill N. Amessoudji, Amy Li, Zhanhai Meyer, Keith C. |
author_facet | Tsao, Francis H.C. Barnes, Jill N. Amessoudji, Amy Li, Zhanhai Meyer, Keith C. |
author_sort | Tsao, Francis H.C. |
collection | PubMed |
description | Aging-related protein misfolding and aggregation may play critical roles in the pathogenesis of numerous diseases. In the brain, extracellular aggregated amyloid-β (Aβ) is closely related to the death of neurons in individuals with Alzheimer’s disease (AD). Albumin-Aβ binding is important in preventing Aβ fibril aggregation. However, because albumin is the most abundant and important antioxidant in the circulation, aging-related oxidative stress could have a significant effect on the molecular conformation and binding capacities of albumin. To investigate the link between misfolded albumin and AD, we developed fluorescent assays to determine the effects of misfolded albumin on membrane integrity in the presence of a lipolytic, inflammatory response-like enzyme, secretory phospholipase A2 (sPLA2). We found that misfolded albumin increased degradation of phospholipids in highly fluid bilayer membranes in the presence of sPLA2 due to hydrophobic effects of misfolded albumin. High amounts of misfolded albumin were present in sera of elderly (average 74 years) versus young (average 24 years) subjects (p < 0.0001). Albumin in cerebrospinal fluid (CSF) of elderly subjects, though present in small concentrations, had a 2- to 3-fold increased capacity to promote sPLA2-catalyzed membrane phospholipid degradation as compared with the same amount of albumin in serum (p < 0.0001). In addition, the fatty acid binding capacity of albumin in CSF from female subjects was considerably lower than values obtained for men, especially for individuals diagnosed with AD (p = 0.0006). This study suggests that inflammation, misfolded albumin and/or other dysfunctional proteins, and changes in membrane fluidity could alter cell membrane integrity and homeostasis and contribute to the pathogenesis of aging-related dementia and AD. |
format | Online Article Text |
id | pubmed-7175925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-71759252020-04-23 Aging-Related and Gender Specific Albumin Misfolding in Alzheimer’s Disease Tsao, Francis H.C. Barnes, Jill N. Amessoudji, Amy Li, Zhanhai Meyer, Keith C. J Alzheimers Dis Rep Research Report Aging-related protein misfolding and aggregation may play critical roles in the pathogenesis of numerous diseases. In the brain, extracellular aggregated amyloid-β (Aβ) is closely related to the death of neurons in individuals with Alzheimer’s disease (AD). Albumin-Aβ binding is important in preventing Aβ fibril aggregation. However, because albumin is the most abundant and important antioxidant in the circulation, aging-related oxidative stress could have a significant effect on the molecular conformation and binding capacities of albumin. To investigate the link between misfolded albumin and AD, we developed fluorescent assays to determine the effects of misfolded albumin on membrane integrity in the presence of a lipolytic, inflammatory response-like enzyme, secretory phospholipase A2 (sPLA2). We found that misfolded albumin increased degradation of phospholipids in highly fluid bilayer membranes in the presence of sPLA2 due to hydrophobic effects of misfolded albumin. High amounts of misfolded albumin were present in sera of elderly (average 74 years) versus young (average 24 years) subjects (p < 0.0001). Albumin in cerebrospinal fluid (CSF) of elderly subjects, though present in small concentrations, had a 2- to 3-fold increased capacity to promote sPLA2-catalyzed membrane phospholipid degradation as compared with the same amount of albumin in serum (p < 0.0001). In addition, the fatty acid binding capacity of albumin in CSF from female subjects was considerably lower than values obtained for men, especially for individuals diagnosed with AD (p = 0.0006). This study suggests that inflammation, misfolded albumin and/or other dysfunctional proteins, and changes in membrane fluidity could alter cell membrane integrity and homeostasis and contribute to the pathogenesis of aging-related dementia and AD. IOS Press 2020-03-30 /pmc/articles/PMC7175925/ /pubmed/32328565 http://dx.doi.org/10.3233/ADR-200168 Text en © 2020 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Report Tsao, Francis H.C. Barnes, Jill N. Amessoudji, Amy Li, Zhanhai Meyer, Keith C. Aging-Related and Gender Specific Albumin Misfolding in Alzheimer’s Disease |
title | Aging-Related and Gender Specific Albumin Misfolding in Alzheimer’s Disease |
title_full | Aging-Related and Gender Specific Albumin Misfolding in Alzheimer’s Disease |
title_fullStr | Aging-Related and Gender Specific Albumin Misfolding in Alzheimer’s Disease |
title_full_unstemmed | Aging-Related and Gender Specific Albumin Misfolding in Alzheimer’s Disease |
title_short | Aging-Related and Gender Specific Albumin Misfolding in Alzheimer’s Disease |
title_sort | aging-related and gender specific albumin misfolding in alzheimer’s disease |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175925/ https://www.ncbi.nlm.nih.gov/pubmed/32328565 http://dx.doi.org/10.3233/ADR-200168 |
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