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

Michael Ewers, Hikmet F. Nural, Cathal Walsh, Thomas Meindl, Stefan J. Teipel, Katharina Buerger, Ping He, Yong Shen, Harald Hampel

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)373-381
Number of pages9
JournalJournal of Alzheimer's Disease
Volume25
Issue number2
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • BACE1
  • cerebrospinal fluid
  • hippocampus
  • β-secretase

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