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Cerebrospinal fluid BACE1 activity and markers of amyloid precursor protein metabolism and axonal degeneration in Alzheimer's disease
Author(s) -
Perneczky Robert,
Alexopoulos Panagiotis
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.09.006
Subject(s) - cerebrospinal fluid , amyloid precursor protein , amyloid precursor protein secretase , dementia , alzheimer's disease , alzheimer's disease neuroimaging initiative , medicine , amyloid (mycology) , tau protein , disease , endocrinology , pathology , neuroscience , psychology
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 tau 181 in all groups but the progressive MCI group. There were no correlations for CSF amyloid β (Aβ) 1‐42 or for plasma Aβ 1‐42 and Aβ 1‐40 . Conclusions The consistent correlation between BACE1 activity and sAPPβ supports their role as biomarkers of target engagement in clinical trials on BACE1 inhibition.