The Scientific World Journal Volume 2012, Article ID 712048, 6 pages doi:10.1100/2012/712048 The cientificWorldJOURNAL Clinical Study Cerebrospinal Fluid BACE1 Activity and Brain Amyloid Load in Alzheimer’s Disease Timo Grimmer, 1 Panagiotis Alexopoulos, 1 Amalia Tsolakidou, 1 Liang-Hao Guo, 1 Gjermund Henriksen, 2 Behrooz H. Yousefi, 2 Hans F¨ orstl, 1 Christian Sorg, 1 Alexander Kurz, 1 Alexander Drzezga, 2 and Robert Perneczky 1 1 Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universit¨ at M¨ unchen, Ismaninger Street 22, 81675 M¨ unchen, Germany 2 Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universit¨ at M¨ unchen, Ismaninger Street 22, 81675 M¨ unchen, Germany Correspondence should be addressed to Robert Perneczky, robert.perneczky@lrz.tum.de Received 17 October 2011; Accepted 2 November 2011 Academic Editors: E. Ghebremedhin and D. R. Thal Copyright © 2012 Timo Grimmer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 ([ 11 C]PIB PET). [ 11 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 [ 11 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. 1. Introduction The cerebrospinal fluid (CSF) is in close contact with the extracellular space of the central nervous system; therefore, pathological changes such as those due to neurodegeneration are reflected in CSF and alterations of biomarkers can yield important mechanistic and diagnostic information on disease processes. In Alzheimer’s disease (AD), a growing number of CSF biomarkers are studied, some of which mirror important events in the pathogenic cascade. These markers include several indicators of changes related to the amyloid cascade such as amyloid β 42 (Aβ42), total tau and phosphorylated tau [1]. The amyloid hypothesis of AD argues a cerebral accumulation of amyloid as primary driver of AD pathogenesis, including amyloid plaque deposition, neurofibrillary tangle formation, synapse loss, and neuronal cell death [2]. The amyloid deposits of insoluble protein material mainly contain high levels of the 40 and 42 amino acid long Aβ, which is produced through the cleavage of a membrane-bound amyloid precursor protein (APP) by the β- and γ-secretases. The cleavage of APP by the main cerebral β-secretase (β-site APP-cleaving enzyme 1, BACE1) [3] occurs at the N-terminus of the Aβ-domain and results in secreted soluble APP β (sAPPβ) and a C-terminal fragment (C99) [4], which subsequently undergoes cleavage by γ- secretase producing Aβ. The crucial role of BACE1 in AD pathogenesis is highlighted by its increased enzyme activity and protein concentration in AD brains [5]. Several previous studies have shown that BACE1 activity can readily be detected in CSF with activity increases in mild cognitive impairment (MCI) and clinically diagnosable AD [6–8]. The relevance of BACE1 in the amyloid cascade is also underscored by its positive association with the CSF products of APP cleavage, including Aβ40 and sAPPβ [9]. Therefore,