Abstract
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.
Highlights
As people age, the aging process, cardiovascular disease (Prince, 2015; Yang et al, 2018) and other factors (Winblad et al, 2016; Yang et al, 2019) may increase the risk of Alzheimer’s disease (AD)
We examined the concentrations of plasma Aβ1−40 and Aβ1−42 at different time points and assessed their associations with apo-lipoprotein E gene (APOE) genetic status and disease severity in fresh blood samples obtained from AD patients
There was no significant difference in the ratio of AD patients having an increase in Aβ1−40 level between the APOE4(+) and APOE4(−) groups (p = 0.422)
Summary
The aging process, cardiovascular disease (Prince, 2015; Yang et al, 2018) and other factors (Winblad et al, 2016; Yang et al, 2019) may increase the risk of Alzheimer’s disease (AD). It has been estimated that 46.8 million people worldwide were living with dementia in 2015, and this number is expected to reach 74.7 million by 2030 and 131.5 million by 2050 (Hebert et al, 2004; Prince, 2015). AD is the most common form of dementia worldwide (Hebert et al, 2004; Prince, 2015; Yang et al, 2019). Aβ1−42 and Aβ1−40 in cerebrospinal fluid (CSF) are regarded to be biomarkers in the diagnosis of AD (Strozyk et al, 2003; Tapiola et al, 2009), consensus with regards to the standard procedures for detecting Aβ1−42 and Aβ1−40 concentrations in CSF is currently lacking. Given the invasiveness of obtaining CSF for examinations and inter-laboratory variability in the detection of Aβ1−42 and Aβ1−40 concentrations (Mattsson et al, 2010, 2012, 2013), CSF examinations for Aβ1−40 and Aβ1−42 level are not always practical
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