The Aβ42:Aβ40 ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction
The pathophysiological role of Aβ42 oligomers in the onset of Alzheimer’s disease (AD) is heavily disputed, pivoting research toward investigating mixed oligomers composed of Aβ42 and Aβ40, which is more abundant but less aggregation-prone. This study investigates Aβ42:Aβ40 oligomers in different ra...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2024.1516093/full |
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| author | Annika Haessler Stefanie Gier Nathalie Jung Maike Windbergs |
| author_facet | Annika Haessler Stefanie Gier Nathalie Jung Maike Windbergs |
| author_sort | Annika Haessler |
| collection | DOAJ |
| description | The pathophysiological role of Aβ42 oligomers in the onset of Alzheimer’s disease (AD) is heavily disputed, pivoting research toward investigating mixed oligomers composed of Aβ42 and Aβ40, which is more abundant but less aggregation-prone. This study investigates Aβ42:Aβ40 oligomers in different ratios, examining their adverse effects on endothelial cells, neurons, astroglia, and microglia, as well as in a human blood–brain barrier (BBB) model. Combining label-free Raman microscopy with complementary imaging techniques and biochemical assays, we show the prominent impact of Aβ40 on Aβ42 fibrillation, suggesting an inhibitory effect on aggregation. Mixed oligomers, especially with low proportions of Aβ42, were equally detrimental as pure Aβ42 oligomers regarding cell viability, functionality, and metabolism. They also differentially affected lipid droplet metabolism in BBB-associated microglia, indicating distinct pathophysiological responses. Our findings demonstrate the overarching significance of the Aβ42:Aβ40 ratio in Aβ oligomers, challenging the traditional focus on Aβ42 in AD research. |
| format | Article |
| id | doaj-art-5cea5aed3e6347ca8ee6311f66dcadd2 |
| institution | OA Journals |
| issn | 1662-5102 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj-art-5cea5aed3e6347ca8ee6311f66dcadd22025-08-20T01:55:15ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022024-12-011810.3389/fncel.2024.15160931516093The Aβ42:Aβ40 ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunctionAnnika HaesslerStefanie GierNathalie JungMaike WindbergsThe pathophysiological role of Aβ42 oligomers in the onset of Alzheimer’s disease (AD) is heavily disputed, pivoting research toward investigating mixed oligomers composed of Aβ42 and Aβ40, which is more abundant but less aggregation-prone. This study investigates Aβ42:Aβ40 oligomers in different ratios, examining their adverse effects on endothelial cells, neurons, astroglia, and microglia, as well as in a human blood–brain barrier (BBB) model. Combining label-free Raman microscopy with complementary imaging techniques and biochemical assays, we show the prominent impact of Aβ40 on Aβ42 fibrillation, suggesting an inhibitory effect on aggregation. Mixed oligomers, especially with low proportions of Aβ42, were equally detrimental as pure Aβ42 oligomers regarding cell viability, functionality, and metabolism. They also differentially affected lipid droplet metabolism in BBB-associated microglia, indicating distinct pathophysiological responses. Our findings demonstrate the overarching significance of the Aβ42:Aβ40 ratio in Aβ oligomers, challenging the traditional focus on Aβ42 in AD research.https://www.frontiersin.org/articles/10.3389/fncel.2024.1516093/fullAlzheimer’s diseaseAβ oligomersblood–brain barrierRaman microscopylipid dropletsAβ42:Aβ40 |
| spellingShingle | Annika Haessler Stefanie Gier Nathalie Jung Maike Windbergs The Aβ42:Aβ40 ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction Frontiers in Cellular Neuroscience Alzheimer’s disease Aβ oligomers blood–brain barrier Raman microscopy lipid droplets Aβ42:Aβ40 |
| title | The Aβ42:Aβ40 ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction |
| title_full | The Aβ42:Aβ40 ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction |
| title_fullStr | The Aβ42:Aβ40 ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction |
| title_full_unstemmed | The Aβ42:Aβ40 ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction |
| title_short | The Aβ42:Aβ40 ratio modulates aggregation in beta-amyloid oligomers and drives metabolic changes and cellular dysfunction |
| title_sort | aβ42 aβ40 ratio modulates aggregation in beta amyloid oligomers and drives metabolic changes and cellular dysfunction |
| topic | Alzheimer’s disease Aβ oligomers blood–brain barrier Raman microscopy lipid droplets Aβ42:Aβ40 |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2024.1516093/full |
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