Tags

Type your tag names separated by a space and hit enter

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Psychiatry, Alzheimer Memorial Center, Ludwig-Maximilian University, Munich, Germany.

    , , , , , ,

    Source

    Brain : a journal of neurology 131:Pt 5 2008 May pg 1252-8

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Amyloid Precursor Protein Secretases
    Amyloid beta-Peptides
    Apolipoproteins E
    Aspartic Acid Endopeptidases
    Biomarkers
    Cognition Disorders
    Female
    Genotype
    Humans
    Male
    Middle Aged
    Peptide Fragments

    Pub Type(s)

    Journal Article
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18334538

    Citation

    Ewers, Michael, et al. "Increased CSF-BACE 1 Activity Is Associated With ApoE-epsilon 4 Genotype in Subjects With Mild Cognitive Impairment and Alzheimer's Disease." Brain : a Journal of Neurology, vol. 131, no. Pt 5, 2008, pp. 1252-8.
    Ewers M, Zhong Z, Bürger K, et al. Increased CSF-BACE 1 activity is associated with ApoE-epsilon 4 genotype in subjects with mild cognitive impairment and Alzheimer's disease. Brain. 2008;131(Pt 5):1252-8.
    Ewers, M., Zhong, Z., Bürger, K., Wallin, A., Blennow, K., Teipel, S. J., ... Hampel, H. (2008). Increased CSF-BACE 1 activity is associated with ApoE-epsilon 4 genotype in subjects with mild cognitive impairment and Alzheimer's disease. Brain : a Journal of Neurology, 131(Pt 5), pp. 1252-8. doi:10.1093/brain/awn034.
    Ewers M, et al. Increased CSF-BACE 1 Activity Is Associated With ApoE-epsilon 4 Genotype in Subjects With Mild Cognitive Impairment and Alzheimer's Disease. Brain. 2008;131(Pt 5):1252-8. PubMed PMID: 18334538.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Increased CSF-BACE 1 activity is associated with ApoE-epsilon 4 genotype in subjects with mild cognitive impairment and Alzheimer's disease. AU - Ewers,Michael, AU - Zhong,Zhenyu, AU - Bürger,Katharina, AU - Wallin,Anders, AU - Blennow,Kaj, AU - Teipel,Stefan J, AU - Shen,Yong, AU - Hampel,Harald, Y1 - 2008/03/11/ PY - 2008/3/13/pubmed PY - 2008/6/17/medline PY - 2008/3/13/entrez SP - 1252 EP - 8 JF - Brain : a journal of neurology JO - Brain VL - 131 IS - Pt 5 N2 - 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. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/18334538/Increased_CSF_BACE_1_activity_is_associated_with_ApoE_epsilon_4_genotype_in_subjects_with_mild_cognitive_impairment_and_Alzheimer's_disease_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awn034 DB - PRIME DP - Unbound Medicine ER -