title: Increased CSF-BACE 1 activity is associated with ApoE-epsilon 4 genotype in subjects with mild cognitive impairment and Alzheimer's disease.
abstract: 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(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(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(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.
authors.affiliation: Department of Psychiatry, Alzheimer Memorial Center, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ewers
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhong
authors.forename: Katharina
authors.initials: K
authors.lastname: Bürger
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.forename: Yong
authors.initials: Y
authors.lastname: Shen
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics*; D016282:Aspartic Acid Endopeptidases / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human