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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.

Artikel i vetenskaplig tidskrift
Författare Michael Ewers
Zhenyu Zhong
Katharina Bürger
Anders Wallin
Kaj Blennow
Stefan J Teipel
Yong Shen
Harald Hampel
Publicerad i Brain : a journal of neurology
Volym 131
Nummer/häfte Pt 5
Sidor 1252-8
ISSN 1460-2156
Publiceringsår 2008
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 1252-8
Språk en
Länkar dx.doi.org/10.1093/brain/awn034
Ämnesord Aged, Aged, 80 and over, Alzheimer Disease, cerebrospinal fluid, genetics, Amyloid Precursor Protein Secretases, cerebrospinal fluid, Amyloid beta-Protein, cerebrospinal fluid, Apolipoproteins E, genetics, Aspartic Endopeptidases, cerebrospinal fluid, Biological Markers, cerebrospinal fluid, Cognition Disorders, cerebrospinal fluid, genetics, Female, Genotype, Humans, Male, Middle Aged, Peptide Fragments, cerebrospinal fluid
Ämneskategorier Psykiatri

Sammanfattning

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.

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