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

Dement Geriatr Cogn Disord. 2018;45(3-4):152-161. doi: 10.1159/000488481. Epub 2018 May 22.

Abstract

Background/aims: The utility of β-site amyloid-β precursor protein (AβPP) cleaving enzyme 1 (BACE1) activity and soluble AβPP β (sAβPPβ) levels in cerebrospinal fluid (CSF) in detecting Alzheimer's disease (AD) is still elusive.

Methods: BACE1 activity and sAβPPβ 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 18F-fluorodeoxyglucose positron emission tomography (FDG PET) data, ordinal regression models were employed to compare the contribution of BACE1 and sAβPPβ 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. sAβPPβ 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.

Keywords: BACE1; Biomarker candidate; Dementia; Mild cognitive impairment; sAβPPβ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / diagnosis
  • Amyloid Precursor Protein Secretases / cerebrospinal fluid*
  • Amyloid beta-Protein Precursor / cerebrospinal fluid*
  • Aspartic Acid Endopeptidases / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction* / cerebrospinal fluid
  • Cognitive Dysfunction* / diagnosis
  • Diagnosis, Differential
  • Female
  • Fluorodeoxyglucose F18 / pharmacology
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / pharmacology

Substances

  • Amyloid beta-Protein Precursor
  • Biomarkers
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human