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. 2024 Jul 30;25(15):8354.
doi: 10.3390/ijms25158354.

Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer's Disease and Frontotemporal Dementia: A Pilot Study

Claudia Saraceno  1 , Carlo Cervellati  2 , Alessandro Trentini  3 , Daniela Crescenti  1 , Antonio Longobardi  1 , Andrea Geviti  4 , Natale Salvatore Bonfiglio  4 , Sonia Bellini  1 , Roland Nicsanu  1 , Silvia Fostinelli  5 , Gianmarco Mola  2 , Raffaella Riccetti  3 , Davide Vito Moretti  6 , Orazio Zanetti  7 , Giuliano Binetti  5 , Giovanni Zuliani  2 , Roberta Ghidoni  1
Affiliations

Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer's Disease and Frontotemporal Dementia: A Pilot Study

Claudia Saraceno et al. Int J Mol Sci. .

Abstract

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two major neurodegenerative diseases causing dementia. Due to similar clinical phenotypes, differential diagnosis is challenging without specific biomarkers. Beta-site Amyloid Precursor Protein cleaving enzyme 1 (BACE1) is a β-secretase pivotal in AD pathogenesis. In AD and mild cognitive impairment subjects, BACE1 activity is increased in brain/cerebrospinal fluid, and plasma levels appear to reflect those in the brain. In this study, we aim to evaluate serum BACE1 activity in FTD, since, to date, there is no evidence about its role. The serum of 30 FTD patients and 30 controls was analyzed to evaluate (i) BACE1 activity, using a fluorescent assay, and (ii) Glial Fibrillary Acid Protein (GFAP) and Neurofilament Light chain (NfL) levels, using a Simoa kit. As expected, a significant increase in GFAP and NfL levels was observed in FTD patients compared to controls. Serum BACE1 activity was not altered in FTD patients. A significant increase in serum BACE1 activity was shown in AD vs. FTD and controls. Our results support the hypothesis that serum BACE1 activity is a potential biomarker for the differential diagnosis between AD and FTD.

Keywords: Alzheimer’s disease; BACE1; GFAP; NfL; biomarker; differential diagnosis; frontotemporal dementia; serum.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
BACE1 activity (a) and the levels of GFAP (b) and NfL (c) in the serum of CTRL (n = 30) and FTD patients (n = 30). No differences were observed in BACE1 activity between the two groups. A significant increase in GFAP and NfL levels was shown in FTD patients compared to CTRL. Mean ± SEM; * p < 0.05 and **** p < 0.0001.
Figure 2
Figure 2
BACE1 activity (a) and the levels of GFAP (b) and NfL (c) in the serum of CTRL (n = 60), AD (n = 31), and FTD (n = 30) patients. A significant increase in BACE1 activity was shown in AD patients compared to CTRL and FTD patients. No differences were observed between CTRL and FTD patients. A significant increase in both GFAP and NfL levels was observed in AD and FTD patients compared to CTRL. Moreover, a significant increase in GFAP levels was shown in AD compared to FTD patients. No differences of NfL levels were observed between AD and FTD patients. Mean ± SEM; * p < 0.05, ** p < 0.01, and *** p < 0.001.
Figure 3
Figure 3
Classification tree obtained for AD (n = 31) vs. FTD (n = 30) patients based on BACE1 activity and GFAP levels in serum. BACE1 activity resulted in being able to discriminate AD from FTD patients with very high percentage (95.7%).
See this image and copyright information in PMC

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