Cerebrospinal fluid BACE1 activity and brain amyloid load in Alzheimer's disease
Author(s)
Type
Journal Article
Abstract
The secretase BACE1 is fundamentally involved in the development of cerebral amyloid pathology in Alzheimer's disease (AD). It has not been studied so far to what extent BACE1 activity in cerebrospinal fluid (CSF) mirrors in vivo amyloid load in AD. We explored associations between CSF BACE1 activity and fibrillar amyloid pathology as measured by carbon-11-labelled Pittsburgh Compound B positron emission tomography ([(1)(1)C]PIB PET). [(1)(1)C]PIB and CSF studies were performed in 31 patients with AD. Voxel-based linear regression analysis revealed significant associations between CSF BACE1 activity and [(1)(1)C]PIB tracer uptake in the bilateral parahippocampal region, the thalamus, and the pons. Our study provides evidence for a brain region-specific correlation between CSF BACE1 activity and in-vivo fibrillar amyloid pathology in AD. Associations were found in areas close to the brain ventricles, which may have important implications for the use of BACE1 in CSF as a marker for AD pathology and for antiamyloid treatment monitoring.
Date Issued
2012-01-01
Date Acceptance
2011-11-02
Citation
The Scientific World Journal, 2012, 2012
ISSN
1537-744X
Publisher
Hindawi Publishing Corporation
Journal / Book Title
The Scientific World Journal
Volume
2012
Copyright Statement
© 2012 Timo Grimmer et al. This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/22272179
Subjects
Aged Alzheimer Disease/*cerebrospinal fluid/enzymology/pathology Amyloid/*analysis Amyloid Precursor Protein Secretases/*cerebrospinal fluid Aspartic Acid Endopeptidases/*cerebrospinal fluid Biological Markers/cerebrospinal fluid Brain/pathology *Brain Chemistry Female Hippocampus/chemistry Humans Male Neuroimaging Pons/chemistry Positron-Emission Tomography Thalamus/chemistry
Notes
Grimmer, Timo Alexopoulos, Panagiotis Tsolakidou, Amalia Guo, Liang-Hao Henriksen, Gjermund Yousefi, Behrooz H Forstl, Hans Sorg, Christian Kurz, Alexander Drzezga, Alexander Perneczky, Robert England ScientificWorldJournal. 2012;2012:712048. doi: 10.1100/2012/712048. Epub 2012 Jan 3. The secretase BACE1 is fundamentally involved in the development of cerebral amyloid pathology in Alzheimer's disease (AD). It has not been studied so far to what extent BACE1 activity in cerebrospinal fluid (CSF) mirrors in vivo amyloid load in AD. We explored associations between CSF BACE1 activity and fibrillar amyloid pathology as measured by carbon-11-labelled Pittsburgh Compound B positron emission tomography ([(1)(1)C]PIB PET). [(1)(1)C]PIB and CSF studies were performed in 31 patients with AD. Voxel-based linear regression analysis revealed significant associations between CSF BACE1 activity and [(1)(1)C]PIB tracer uptake in the bilateral parahippocampal region, the thalamus, and the pons. Our study provides evidence for a brain region-specific correlation between CSF BACE1 activity and in-vivo fibrillar amyloid pathology in AD. Associations were found in areas close to the brain ventricles, which may have important implications for the use of BACE1 in CSF as a marker for AD pathology and for antiamyloid treatment monitoring.
Article Number
712048
Date Publish Online
2012-01-01