Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s Disease
Amyloid-beta (Aβ) is produced by the cleavage of amyloid precursor proteins in the cell membrane by β-secretase and γ-secretase into a monomeric form with peptides of different lengths such as Aβ1–40 or Aβ1–42, which is then transformed into oligomeric and fibril forms and is considered to be one of...
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00768/full |
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| author | Yuan-Han Yang Yuan-Han Yang Yuan-Han Yang Yuan-Han Yang Yuan-Han Yang Ling-Chun Huang Ling-Chun Huang Sun-Wung Hsieh Sun-Wung Hsieh Li-Ju Huang Li-Ju Huang |
| author_facet | Yuan-Han Yang Yuan-Han Yang Yuan-Han Yang Yuan-Han Yang Yuan-Han Yang Ling-Chun Huang Ling-Chun Huang Sun-Wung Hsieh Sun-Wung Hsieh Li-Ju Huang Li-Ju Huang |
| author_sort | Yuan-Han Yang |
| collection | DOAJ |
| description | Amyloid-beta (Aβ) is produced by the cleavage of amyloid precursor proteins in the cell membrane by β-secretase and γ-secretase into a monomeric form with peptides of different lengths such as Aβ1–40 or Aβ1–42, which is then transformed into oligomeric and fibril forms and is considered to be one of the hallmarks of Alzheimer’s disease (AD). The plasma concentrations of Aβ1–40 and Aβ1–42 are unstable after blood samples have been obtained. In order to examine the dynamic changes of plasma Aβ1–42 and Aβ1–40 in blood samples, we used fresh blood samples in ethylenediaminetetraacetic acid tubes from 32 clinically diagnosed AD patients. Each sample was subdivided into eight sub-samples, and levels of Aβ1–40 and Aβ1–42 were measured at 0 (baseline), 0.5, 1, 2, 3, 5, 8, and 24 h, respectively. All samples were incubated at 37°C before being measuring. The results showed that compared to baseline, 87.5 and 62.5% of the patients had higher plasma levels of Aβ1–42 and Aβ1–40 at 24 h, respectively. The patients with an increased amyloid level did not have a significantly different apo-lipoprotein E4 allele (APOE4) gene status for either Aβ1–40 (p = 0.422) or Aβ1–42 (p = 1.000). However, for plasma Aβ1–42, the APOE4 carriers had a significantly lower level than the non-carriers at baseline [31.2 ± 6.5 (mean ± SD) ng/ml vs. 50.4 ± 47.7 ng/ml, p = 0.031] and 0.5 h (37.5 ± 7.6 ng/ml vs. 51.9 ± 30.8 ng/ml, p = 0.043). There were no significant differences between the APOE4 carriers and non-carriers in plasma Aβ1–42 concentration at 1, 2, 3, 5, 8, and 24 h (p = 0.112, p = 0.086, p = 0.112, p = 0.263, p = 0.170 and p = 0.621, respectively). The Aβ1–40 level was related to disease severity as assessed using the clinical dementia rating (CDR) scale. Patients with advanced stages of dementia (CDR = 1 and CDR = 2) had a significantly higher Aβ1–40 level compared to those with very mild stage dementia (CDR = 0.5) at all time points (p < 0.05) except for 24 h (p = 0.059). Our findings illustrate the effects of APOE4 status on dynamic changes in plasma Aβ1–40 and Aβ1–42 levels, and significant associations between Aβ1–40 level and disease severity. Further studies are needed to investigate the exact mechanisms of how APOE4 affects the dynamic changes in plasma Aβ1–40 and Aβ1–42, and the association between Aβ1–40 and advanced dementia. |
| first_indexed | 2024-12-11T13:03:58Z |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-11T13:03:58Z |
| publishDate | 2020-08-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-d3834ca2494b4917a1f8c77bfab66ed82022-12-22T01:06:22ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-08-01810.3389/fcell.2020.00768549912Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s DiseaseYuan-Han Yang0Yuan-Han Yang1Yuan-Han Yang2Yuan-Han Yang3Yuan-Han Yang4Ling-Chun Huang5Ling-Chun Huang6Sun-Wung Hsieh7Sun-Wung Hsieh8Li-Ju Huang9Li-Ju Huang10Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanCenter of Teaching and Research, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of and Master’s Program in Neurology, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanNeuroscience Research Center, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanDepartment of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanCenter of Teaching and Research, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanAmyloid-beta (Aβ) is produced by the cleavage of amyloid precursor proteins in the cell membrane by β-secretase and γ-secretase into a monomeric form with peptides of different lengths such as Aβ1–40 or Aβ1–42, which is then transformed into oligomeric and fibril forms and is considered to be one of the hallmarks of Alzheimer’s disease (AD). The plasma concentrations of Aβ1–40 and Aβ1–42 are unstable after blood samples have been obtained. In order to examine the dynamic changes of plasma Aβ1–42 and Aβ1–40 in blood samples, we used fresh blood samples in ethylenediaminetetraacetic acid tubes from 32 clinically diagnosed AD patients. Each sample was subdivided into eight sub-samples, and levels of Aβ1–40 and Aβ1–42 were measured at 0 (baseline), 0.5, 1, 2, 3, 5, 8, and 24 h, respectively. All samples were incubated at 37°C before being measuring. The results showed that compared to baseline, 87.5 and 62.5% of the patients had higher plasma levels of Aβ1–42 and Aβ1–40 at 24 h, respectively. The patients with an increased amyloid level did not have a significantly different apo-lipoprotein E4 allele (APOE4) gene status for either Aβ1–40 (p = 0.422) or Aβ1–42 (p = 1.000). However, for plasma Aβ1–42, the APOE4 carriers had a significantly lower level than the non-carriers at baseline [31.2 ± 6.5 (mean ± SD) ng/ml vs. 50.4 ± 47.7 ng/ml, p = 0.031] and 0.5 h (37.5 ± 7.6 ng/ml vs. 51.9 ± 30.8 ng/ml, p = 0.043). There were no significant differences between the APOE4 carriers and non-carriers in plasma Aβ1–42 concentration at 1, 2, 3, 5, 8, and 24 h (p = 0.112, p = 0.086, p = 0.112, p = 0.263, p = 0.170 and p = 0.621, respectively). The Aβ1–40 level was related to disease severity as assessed using the clinical dementia rating (CDR) scale. Patients with advanced stages of dementia (CDR = 1 and CDR = 2) had a significantly higher Aβ1–40 level compared to those with very mild stage dementia (CDR = 0.5) at all time points (p < 0.05) except for 24 h (p = 0.059). Our findings illustrate the effects of APOE4 status on dynamic changes in plasma Aβ1–40 and Aβ1–42 levels, and significant associations between Aβ1–40 level and disease severity. Further studies are needed to investigate the exact mechanisms of how APOE4 affects the dynamic changes in plasma Aβ1–40 and Aβ1–42, and the association between Aβ1–40 and advanced dementia.https://www.frontiersin.org/article/10.3389/fcell.2020.00768/fullamyloid-beta-proteinAlzheimer’s diseaseAPOECDRdementia |
| spellingShingle | Yuan-Han Yang Yuan-Han Yang Yuan-Han Yang Yuan-Han Yang Yuan-Han Yang Ling-Chun Huang Ling-Chun Huang Sun-Wung Hsieh Sun-Wung Hsieh Li-Ju Huang Li-Ju Huang Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s Disease Frontiers in Cell and Developmental Biology amyloid-beta-protein Alzheimer’s disease APOE CDR dementia |
| title | Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s Disease |
| title_full | Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s Disease |
| title_fullStr | Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s Disease |
| title_full_unstemmed | Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s Disease |
| title_short | Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s Disease |
| title_sort | dynamic blood concentrations of aβ1 40 and aβ1 42 in alzheimer s disease |
| topic | amyloid-beta-protein Alzheimer’s disease APOE CDR dementia |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00768/full |
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