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ABSTRACT: Background
Beta-site APP cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in amyloid-β (Aβ) plaques formation. BACE1 activity is increased in brains of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and plasma levels of BACE1 appears to reflect those in the brains.Objective
In this work, we investigated the role of serum BACE1 activity as biomarker for AD, estimating the diagnostic accuracy of the assay and assessing the correlation of BACE1 activity with levels of Aβ1 - 40, Aβ1 - 42, and Aβ40/42 ratio in serum, known biomarkers of brain amyloidosis.Methods
Serum BACE1 activity and levels of Aβ1 - 40, Aβ1 - 42, were assessed in 31 AD, 28 MCI, diagnosed as AD at follow-up (MCI-AD), and 30 controls. The BACE1 analysis was performed with a luciferase assay, where interpolation of relative fluorescence units with a standard curve of concentration reveals BACE1 activity. Serum levels of Aβ1 - 40, Aβ1 - 42 were measured with the ultrasensitive Single Molecule Array technology.Results
BACE1 was increased (higher than 60%) in AD and MCI-AD: a cut-off of 11.04 kU/L discriminated patients with high sensitivity (98.31%) and specificity (100%). Diagnostic accuracy was higher for BACE1 than Aβ40/42 ratio. High BACE1 levels were associated with worse cognitive performance and earlier disease onset, which was anticipated by 8 years in patients with BACE1 values above the median value (> 16.67 kU/L).Conclusion
Our results provide new evidence supporting serum/plasma BACE1 activity as an early biomarker of AD.
SUBMITTER: Nicsanu R
PROVIDER: S-EPMC9198762 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Nicsanu Roland R Cervellati Carlo C Benussi Luisa L Squitti Rosanna R Zanardini Roberta R Rosta Valentina V Trentini Alessandro A Ferrari Clarissa C Saraceno Claudia C Longobardi Antonio A Bellini Sonia S Binetti Giuliano G Zanetti Orazio O Zuliani Giovanni G Ghidoni Roberta R
Journal of Alzheimer's disease : JAD 20220101 1
<h4>Background</h4>Beta-site APP cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in amyloid-β (Aβ) plaques formation. BACE1 activity is increased in brains of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and plasma levels of BACE1 appears to reflect those in the brains.<h4>Objective</h4>In this work, we investigated the role of serum BACE1 activity as biomarker for AD, estimating the diagnostic accuracy of the assay and assessing the correlation of BACE1 activ ...[more]