Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer's disease.

Hdl Handle:
http://hdl.handle.net/10147/207765
Title:
Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer's disease.
Authors:
Ewers, Michael; Cheng, Xin; Zhong, Zhenyu; Nural, Hikmet F; Walsh, Cathal; Meindl, Thomas; Teipel, Stefan J; Buerger, Katharina; He, Ping; Shen, Yong; Hampel, Harald
Affiliation:
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
Citation:
J Alzheimers Dis. 2011;25(2):373-81.
Journal:
Journal of Alzheimer's disease : JAD
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207765
DOI:
10.3233/JAD-2011-091153
PubMed ID:
21460439
Abstract:
The enzyme beta-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-beta1-42 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-beta-related processes.
Language:
eng
MeSH:
Aged; Aged, 80 and over; Alzheimer Disease/*cerebrospinal fluid/*pathology; Amyloid Precursor Protein Secretases/*cerebrospinal fluid; Amyloid beta-Peptides/cerebrospinal fluid; Aspartic Acid Endopeptidases/*cerebrospinal fluid; Female; Functional Laterality; Hippocampus/*pathology; Humans; Linear Models; Magnetic Resonance Imaging; Male; Peptide Fragments/cerebrospinal fluid; tau Proteins/cerebrospinal fluid
ISSN:
1875-8908 (Electronic); 1387-2877 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorEwers, Michaelen_GB
dc.contributor.authorCheng, Xinen_GB
dc.contributor.authorZhong, Zhenyuen_GB
dc.contributor.authorNural, Hikmet Fen_GB
dc.contributor.authorWalsh, Cathalen_GB
dc.contributor.authorMeindl, Thomasen_GB
dc.contributor.authorTeipel, Stefan Jen_GB
dc.contributor.authorBuerger, Katharinaen_GB
dc.contributor.authorHe, Pingen_GB
dc.contributor.authorShen, Yongen_GB
dc.contributor.authorHampel, Haralden_GB
dc.date.accessioned2012-02-01T10:47:50Z-
dc.date.available2012-02-01T10:47:50Z-
dc.date.issued2012-02-01T10:47:50Z-
dc.identifier.citationJ Alzheimers Dis. 2011;25(2):373-81.en_GB
dc.identifier.issn1875-8908 (Electronic)en_GB
dc.identifier.issn1387-2877 (Linking)en_GB
dc.identifier.pmid21460439en_GB
dc.identifier.doi10.3233/JAD-2011-091153en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207765-
dc.description.abstractThe enzyme beta-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-beta1-42 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-beta-related processes.en_GB
dc.language.isoengen_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshAlzheimer Disease/*cerebrospinal fluid/*pathologyen_GB
dc.subject.meshAmyloid Precursor Protein Secretases/*cerebrospinal fluiden_GB
dc.subject.meshAmyloid beta-Peptides/cerebrospinal fluiden_GB
dc.subject.meshAspartic Acid Endopeptidases/*cerebrospinal fluiden_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFunctional Lateralityen_GB
dc.subject.meshHippocampus/*pathologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshLinear Modelsen_GB
dc.subject.meshMagnetic Resonance Imagingen_GB
dc.subject.meshMaleen_GB
dc.subject.meshPeptide Fragments/cerebrospinal fluiden_GB
dc.subject.meshtau Proteins/cerebrospinal fluiden_GB
dc.titleIncreased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer's disease.en_GB
dc.contributor.departmentDiscipline 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.eduen_GB
dc.identifier.journalJournal of Alzheimer's disease : JADen_GB
dc.description.provinceLeinster-

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