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. 2020 Feb;42(1):159-167.
doi: 10.1007/s11357-019-00127-6. Epub 2019 Nov 19.

Serum beta-secretase 1 (BACE1) activity as candidate biomarker for late-onset Alzheimer's disease

Carlo Cervellati  1 , Alessandro Trentini  2 , Valentina Rosta  2 , Angelina Passaro  3 , Cristina Bosi  3 , Juana Maria Sanz  3 , Stefania Bonazzi  3 , Salvatore Pacifico  4 , Davide Seripa  5 , Giuseppe Valacchi  2   6   7 , Remo Guerini  4 , Giovanni Zuliani  3
Affiliations

Serum beta-secretase 1 (BACE1) activity as candidate biomarker for late-onset Alzheimer's disease

Carlo Cervellati et al. Geroscience. 2020 Feb.

Abstract

Beta-secretase (BACE1) is a key enzyme in the formation of amyloid-β; its activity/concentration is increased in brain and cerebrospinal fluid of patients with late-onset Alzheimer's disease (LOAD). Since BACE1 was found also in blood, we evaluated its potential as peripheral biomarker. To this aim, serum BACE1 activity was assessed in 115 subjects with LOAD and 151 controls. We found that BACE1 changed across groups (p < 0.001) with a 25% increase in LOAD versus controls. High levels of BACE1 (IV quartile) were independently associated with the diagnosis of LOAD (OR 2.8; 1.4-5.7). Diagnostic accuracy was 76% for LOAD. Our data suggest that increased BACE1 activity in serum may represent a potential biomarker for LOAD. Additional studies are needed to confirm the usefulness of BACE1, alone or in combination with other markers, in discriminating patients and predicting LOAD onset and progression.

Keywords: BACE1; Blood-based biomarkers; Late-onset Alzheimer’s disease; Mild cognitive impairment; Mixed dementia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Serum BACE1 activity in controls and LOAD. LOAD patients had significantly higher activity of BACE1 compared to controls (p < 0.001), demonstrating almost 25% higher mean values
Fig. 2
Fig. 2
Correlation between serum BACE1 activity and age in the whole sample and within controls or LOAD subsample. In the whole sample (a), BACE1 activity showed a significant correlation with age (r = 0.299, p < 0.001). Considering subject subsamples, we observed a significant correlation in controls (b) (r = 0.280, p < 0.001) but not in patients with LOAD (c)
Fig. 3
Fig. 3
Serum BACE1 activity in controls and LOAD after exclusion of older subjects. After exclusion of older subjects, BACE1 activity was still significantly higher in LOAD
Fig. 4
Fig. 4
Levels of serum BACE1 activity in controls and LOAD, among women (left) and men (right). BACE1 activity was significantly (and similarly) higher in LOAD compared to controls (p < 0.001) in both men and women subsamples
Fig. 5
Fig. 5
Levels of serum BACE1 activity in controls and LOAD, after exclusion of subjects with comorbidities. After exclusion of subjects with comorbidities (hypertension, diabetes, or CVD), BACE1 activity was still significantly higher in LOAD (p < 0.001) compared to controls. As reported in the text, the mean age of the groups considered in this analysis were comparable to each other
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