Cerebrospinal Fluid BACE1 Activity and sAβPPβ as Biomarker Candidates of Alzheimer's Disease

Background/Aims: The utility of beta-site amyloid-beta precursor protein (OPP) cleaving enzyme 1 (BACE1) activity and soluble A beta PP beta (sA beta PP beta) levels in cerebrospinal fluid (CSF) in detecting Alzheimer's disease (AD) is still elusive. Methods: BACE1 activity and sA beta PP beta concentration were measured in patients with AD dementia (n = 56) and mild cognitive impairment (MCI) due to AD (n = 76) with abnormal routine AD CSF markers, in patients with MCI with normal CSF markers (n = 39), and in controls without preclinical AD (n = 48). In a subsample with available F-18-fluorodeoxyglucose positron emission tomography (FDG PET) data, ordinal regression models were employed to compare the contribution of BACE1 and sA beta PP beta to correct diagnostic classification to that of FDG PET. Results: BACE1 activity was significantly higher in patients with MCI due to AD compared to both controls and patients with MCI with normal CSF markers. sA beta PP beta did not differ between any of the studied groups. Interestingly, BACE1 activity was not found to be inferior to FDG PET as predictive covariate in differentiating between the diagnostic groups. Conclusions: Further studies using biomarker-underpinned diagnoses are warranted to shed more light on the potential diagnostic utility of BACE1 activity as AD biomarker candidate in MCI. (C) 2018 S. Karger AG, Basel