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ERIC Number: EJ793225
Record Type: Journal
Publication Date: 2008-May
Pages: 7
Abstractor: Author
Reference Count: 0
ISBN: N/A
ISSN: ISSN-0006-8950
Increased CSF-BACE 1 Activity Is Associated with ApoE-[Epsilon]4 Genotype in Subjects with Mild Cognitive Impairment and Alzheimer's Disease
Ewers, Michael; Zhong, Zhenyu; Burger, Katharina; Wallin, Anders; Blennow, Kaj; Teipel, Stefan J.; Shen, Yong; Hampel, Harald
Brain, v131 n5 p1252-1258 May 2008
The Apolipoprotein (ApoE) [epsilon]4 allele is a major genetic risk factor of Alzheimer's disease, and may affect the production of amyloid beta (A[beta][subscript 1-42]). Recently, we have shown that [beta]-secretase (BACE 1) activity can be reliably detected within the brain and human CSF. Here, we have examined an association between the ApoE genotype and CSF-levels of BACE 1 activity in Alzheimer's disease and mild cognitive impairment (MCI). A total of 148 subjects were included: 60 Alzheimer's disease patients, 51 MCI subjects and 37 elderly healthy controls. The CSF-levels of A[beta][subscript 1-42], BACE 1 activity and BACE protein were measured in all of these subjects. The differences between ApoE-[epsilon]4 carriers and ApoE-[epsilon]4 non-carriers in these CSF-based measures were determined controlling for gender, age and MMSE score. The ApoE-[epsilon]4 genotype was associated with increased BACE 1 activity in both Alzheimer's disease (P = 0.03) and MCI (P = 0.04) subjects. Levels of A[beta][subscript 1-42] were decreased in ApoE-[epsilon]4 carriers in MCI (P = 0.004) but not Alzheimer's disease subjects. This study is the first to demonstrate the association between ApoE-[epsilon]4 and CSF-BACE 1 activity in MCI and Alzheimer's disease subjects. The assessment of BACE 1 in CSF may provide a sensitive measure to detect "in vivo" alterations in the amyloidogenic processing potentially modified by the ApoE genotype.
Oxford University Press. Great Clarendon Street, Oxford, OX2 6DP, UK. Tel: +44-1865-353907; Fax: +44-1865-353485; e-mail: jnls.cust.serv@oxfordjournals.org; Web site: http://brain.oxfordjournals.org/
Publication Type: Journal Articles; Reports - Research
Education Level: N/A
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A