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. 2014 Oct;10(5 Suppl):S425-S429.e1.
doi: 10.1016/j.jalz.2013.09.006. Epub 2013 Nov 13.

Cerebrospinal fluid BACE1 activity and markers of amyloid precursor protein metabolism and axonal degeneration in Alzheimer's disease

Robert Perneczky  1 , Panagiotis Alexopoulos  2 ; Alzheimer's Disease euroimaging Initiative
Affiliations

Cerebrospinal fluid BACE1 activity and markers of amyloid precursor protein metabolism and axonal degeneration in Alzheimer's disease

Robert Perneczky et al. Alzheimers Dement. 2014 Oct.

Abstract

Objective: The objective of this study was to assess cerebrospinal fluid (CSF) β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) activity in relation to Alzheimer's disease (AD) and to correlate the enzyme activity with protein markers of APP metabolism and axonal degeneration.

Methods: BACE1 activity and protein concentrations were measured and analyzed in 342 participants of the Alzheimer's Disease Neuroimaging Initiative, including 99 normal control, 75 stable mild cognitive impairment (MCI), 87 progressive MCI, and 79 AD dementia cases. All statistical analyses were Bonferroni corrected for multiple comparisons.

Results: No significant differences between controls and any of the three patient groups were detected for BACE1 activity and soluble APPβ (sAPPβ) concentrations in CSF. Significant correlations with BACE1 activity were found for CSF APPβ and total tau in all four groups and for CSF phosphorylated tau181 in all groups but the progressive MCI group. There were no correlations for CSF amyloid β (Aβ)1-42 or for plasma Aβ1-42 and Aβ1-40.

Conclusions: The consistent correlation between BACE1 activity and sAPPβ supports their role as biomarkers of target engagement in clinical trials on BACE1 inhibition.

Keywords: Amyloid precursor protein; Amyloid-β; Biomarker; Correlation; Dementia; Diagnosis; Mild cognitive impairment; Prognosis; Tau.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Scatterplots showing the correlations between BACE1 activity and the concentrations of cerebrospinal fluid proteins (rows) in the different study groups (columns) NL: normal controls; sMCI: stable mild cognitive impairment; pMCI: progressive mild cognitive impairment; AD: Alzheimer’s disease; BACE1: beta-site amyloid precursor protein cleaving enzyme 1; sAPPβ: soluble amyloid precursor protein β; tTau: total-Tau; pTau181: phosphorylated Tau181.
See this image and copyright information in PMC

References

    1. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2002;297(5580):353–6. - PubMed
    1. Vassar R. BACE1: the beta-secretase enzyme in Alzheimer’s disease. J Mol Neurosci. 2004;23(1-2):105–14. - PubMed
    1. Zetterberg H, Andreasson U, Hansson O, Wu G, Sankaranarayanan S, Andersson ME, et al. Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease. Arch Neurol. 2008;65(8):1102–7. - PubMed
    1. Zhong Z, Ewers M, Teipel S, Burger K, Wallin A, Blennow K, et al. Levels of beta-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment. Arch gen psychiatry. 2007;64(6):718–26. - PubMed
    1. U S Food and Drug Administration draft guidance for industry, clinical investigators, and Food and Drug Administration staff – design considerations for pivotal clinical investigations for medical devices. Rockwell, MD: Food and Drug Administration; 2011.

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