AUTHOR=Yang Yuan-Han , Huang Ling-Chun , Hsieh Sun-Wung , Huang Li-Ju 

TITLE=Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s Disease

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00768

DOI=10.3389/fcell.2020.00768

ISSN=2296-634X

ABSTRACT=<p>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 Aβ<sub>1–40</sub> or Aβ<sub>1–42</sub>, 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 Aβ<sub>1–40</sub> and Aβ<sub>1–42</sub> are unstable after blood samples have been obtained. In order to examine the dynamic changes of plasma Aβ<sub>1–42</sub> and Aβ<sub>1–40</sub> 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 Aβ<sub>1–40</sub> and Aβ<sub>1–42</sub> 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 Aβ<sub>1–42</sub> and Aβ<sub>1–40</sub> 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 Aβ<sub>1–40</sub> (<italic>p</italic> = 0.422) or Aβ<sub>1–42</sub> (<italic>p</italic> = 1.000). However, for plasma Aβ<sub>1–42</sub>, 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, <italic>p</italic> = 0.031] and 0.5 h (37.5 ± 7.6 ng/ml vs. 51.9 ± 30.8 ng/ml, <italic>p</italic> = 0.043). There were no significant differences between the APOE4 carriers and non-carriers in plasma Aβ<sub>1–42</sub> concentration at 1, 2, 3, 5, 8, and 24 h (<italic>p</italic> = 0.112, <italic>p</italic> = 0.086, <italic>p</italic> = 0.112, <italic>p</italic> = 0.263, <italic>p</italic> = 0.170 and <italic>p</italic> = 0.621, respectively). The Aβ<sub>1–40</sub> 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 Aβ<sub>1–40</sub> level compared to those with very mild stage dementia (CDR = 0.5) at all time points (<italic>p</italic> &lt; 0.05) except for 24 h (<italic>p</italic> = 0.059). Our findings illustrate the effects of APOE4 status on dynamic changes in plasma Aβ<sub>1–40</sub> and Aβ<sub>1–42</sub> levels, and significant associations between Aβ<sub>1–40</sub> level and disease severity. Further studies are needed to investigate the exact mechanisms of how APOE4 affects the dynamic changes in plasma Aβ<sub>1–40</sub> and Aβ<sub>1–42</sub>, and the association between Aβ<sub>1–40</sub> and advanced dementia.</p>