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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):1252-8B

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+Show Affiliations

Department of Psychiatry, Alzheimer Memorial Center, Ludwig-Maximilian University, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -