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Table 2 BACE1 blood-based biomarkers

From: β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification

BACE1 activity (method)

 Antibody

Substrate

Clinical study

Result

ELISA

Anti-BACE1 Ab SECB1&2 [56, 57]

Synthetic peptide substrates containing the β-cleavage site (Calbiochem, EMD, Gibbstown, NJ, USA) [59]

Shen et al. [36]

Plasma BACE1 activity significantly increased by 53.2% in MCI and by 68.9% in AD compared to HC

ELISA

Anti-BACE1 Ab SECB1&2 [56, 57]

Synthetic substate-C-terminally labeled with the fluorescent, Luciferase Yellow, and N-terminally labeled with the quenching, Dabsyl

Cervellati et al. [35]

Increased BACE1 activity in serum of AD

ELISA

Biotinylated detector mAb, diluted in a buffer adapted for the plasma matrix

Kit-based assay EQ 6541–9601-L; Euroimmun AG, Lübeck, Germany [18]

Vergallo et al. [37]

Plasma BACE1 significantly higher in women than in men in cognitively healthy individuals at clinical risk for AD

Solution-based platelet BACE1 assay

 

Fluorogenic substrate (Calbiochem, BACE1 substrate I)

Johnston et al. [39]

17% increase in platelet membrane BACE1 activity in AD compared to HC

Solution-based platelet BACE1 assay

 

Fluorescence-quenching substrate (Calbiochem, Merck, Darmstadt, Germany)

Bermejo-Bescós et al. 2013 [40]

No significant difference in BACE1 activity between MCI and HC

Solution-based platelet BACE1 assay

 

Fluorogenic substrate (Sigma A1472 or Bachem M2465)

Wongchitrat et al. [44]

Baseline platelet membrane BACE1 activity not significantly different between MCI vs HC

Immunoassay

 

Immunoassay kit (CUSABIO, USA)

Vakilian et al. [45]

Elevated plasma levels of BACE1 in AD vs HC

RNA expression analysis

 

Real-time quantitative RT-PCR

Ghafouri-Fard et al. [50]

BACE1 levels significantly high in bipolar disorder

RNA expression analysis

 

Real-time quantitative RT-PCR

Nafisi-Far et al. [51]

BACE1 levels significantly high in schizophrenia

  1. Abbreviations: CSF cerebral spinal fluid, MCI individuals with mild cognitive impairment, AD patients with Alzheimer’s disease dementia, HC cognitively healthy individuals, ELISA enzyme-linked immunosorbent assay, Ab antibody, t-tau total peptide tau protein, amyloid beta, BACE1 beta secretase1