Dynamic Blood Concentrations of Aβ1-40and Aβ1-42in Alzheimer's Disease

Amyloid-beta (A beta) is produced by the cleavage of amyloid precursor proteins in the cell membrane by beta-secretase and gamma-secretase into a monomeric form with peptides of different lengths such as A beta(1-40)or A beta(1-42), 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 A beta(1-40)and A beta(1-42)are unstable after blood samples have been obtained. In order to examine the dynamic changes of plasma A beta(1-42)and A beta(1-40)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 A beta(1-40)and A beta(1-42)were measured at 0 (baseline), 0.5, 1, 2, 3, 5, 8, and 24 h, respectively. All samples were incubated at 37 degrees C before being measuring. The results showed that compared to baseline, 87.5 and 62.5% of the patients had higher plasma levels of A beta(1-42)and A beta(1-40)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 A beta(1-40)(p= 0.422) or A beta(1-42)(p= 1.000). However, for plasma A beta(1-42), 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 A beta(1-42)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 andp= 0.621, respectively). The A beta(1-40)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 A beta(1-40)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 A beta(1-40)and A beta(1-42)levels, and significant associations between A beta(1-40)level and disease severity. Further studies are needed to investigate the exact mechanisms of how APOE4 affects the dynamic changes in plasma A beta(1-40)and A beta(1-42), and the association between A beta(1-40)and advanced dementia.