Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s Disease
Open accessAbstract
Amyloid-beta (Aβ) is produced by the cleavage of amyloid precursor proteins 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 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 hours, respectively. All samples were incubated at 37ºC 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 hours, 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 hours (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 hours (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 hours (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.
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Clinical studies showed that increased levels of plasma Aβ40, but not Aβ42, significantly correlate with a heightened risk of AD.
“Also, clinical studies showed that increased levels of plasma Aβ40, but not Aβ42, significantly correlate with a heightened risk of AD (51,52, 53,54).”
From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [52]
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Alzheimer’s disease as type 3 diabetes: understanding the link and implications
Kciuk, M., Kruczkowska, W., Gałęziewska, J., Wanke, K., Kałuzińska-Kołat, Ż., Aleksandrowicz, M., & Kontek, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252211955 · Cited by 98 · see citing works
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- Authors
- Yang, Y.-H., Huang, L.-C., Hsieh, S.-W., & Huang, L.-J.
- Affiliations
- Kaohsiung Medical University (TW)
- Corresponding author
- Yang, Yuan-Han
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2020-08-11
- Volume
- 8
- Pages
- 768-768
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC7432270
- OpenAlex
- W3048864828
- Cited by
- 39
- References
- 3
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 9 · 2023: 8 · 2022: 4 · 2021: 2 · 2020: 1
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Kaohsiung Medical University
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- Aβ40, amyloid-beta 42, plasma amyloid-beta, Alzheimer's disease, APOE ε4, amyloid precursor protein, amyloid-beta oligomers, biomarkers, blood-brain barrier permeability
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