title: Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer's disease.
abstract: The enzyme β-secretase (BACE1) is essentially involved in the production of cerebral amyloidogenic pathology in Alzheimer's disease (AD). The measurement of BACE1 activity in cerebrospinal fluid (CSF) has been reported, which may render CSF measurement of BACE1 a potential biomarker candidate of AD. In order to investigate whether BACE1 protein activity is correlated with regional brain atrophy in AD, we investigated the association between CSF levels of BACE1 and MRI-assessed hippocampus volume in patients with AD (n = 30). An increase in CSF-BACE1 activity was associated with decreased left and right hippocampus volume corrected for global head volume in the AD patients. Boot-strapped regression analysis showed that increased CSF levels of BACE1 activity were associated with increased CSF concentration of total tau but not amyloid-β1-42 in AD. White matter hyperintensities did not influence the results. BACE1 activity and protein levels were significantly increased in AD compared to 19 elderly healthy controls. Thus, the CSF biomarker candidate of BACE1 activity was associated with hippocampus atrophy in AD in a robust manner and may reflect neurotoxic amyloid-β-related processes.
authors: Discipline of Psychiatry, School of Medicine & Trinity College Institute of Neuroscience, Laboratory of Neuroimaging & Biomarker Research, Trinity College, University of Dublin, The Adelaide and Meath Hospital Incorporating The National Children's Hospital, Tallaght, Ireland. michael.ewers@ucsf.edu
authors: Michael
authors: M
authors: Ewers
authors: Xin
authors: X
authors: Cheng
authors: Zhenyu
authors: Z
authors: Zhong
authors: Hikmet F
authors: HF
authors: Nural
authors: Cathal
authors: C
authors: Walsh
authors: Thomas
authors: T
authors: Meindl
authors: Stefan J
authors: SJ
authors: Teipel
authors: Katharina
authors: K
authors: Buerger
authors: Ping
authors: P
authors: He
authors: Yong
authors: Y
authors: Shen
authors: Harald
authors: H
authors: Hampel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016282:Aspartic Acid Endopeptidases / Q000134:cerebrospinal fluid*; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human