PMID- 18334538
OWN - NLM
STAT- MEDLINE
DCOM- 20080616
LR  - 20151119
IS  - 1460-2156 (Electronic)
IS  - 0006-8950 (Linking)
VI  - 131
IP  - Pt 5
DP  - 2008 May
TI  - Increased CSF-BACE 1 activity is associated with ApoE-epsilon 4 genotype in 
      subjects with mild cognitive impairment and Alzheimer's disease.
PG  - 1252-8
LID - 10.1093/brain/awn034 [doi]
AB  - 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.
FAU - Ewers, Michael
AU  - Ewers M
AD  - Department of Psychiatry, Alzheimer Memorial Center, Ludwig-Maximilian 
      University, Munich, Germany.
FAU - Zhong, Zhenyu
AU  - Zhong Z
FAU - Burger, Katharina
AU  - Burger K
FAU - Wallin, Anders
AU  - Wallin A
FAU - Blennow, Kaj
AU  - Blennow K
FAU - Teipel, Stefan J
AU  - Teipel SJ
FAU - Shen, Yong
AU  - Shen Y
FAU - Hampel, Harald
AU  - Hampel H
LA  - eng
GR  - R01AG025888/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080311
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Biomarkers)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.46 (BACE1 protein, human)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*cerebrospinal fluid/genetics
MH  - Amyloid Precursor Protein Secretases/*cerebrospinal fluid
MH  - Amyloid beta-Peptides/cerebrospinal fluid
MH  - Apolipoproteins E/*genetics
MH  - Aspartic Acid Endopeptidases/*cerebrospinal fluid
MH  - Biomarkers/cerebrospinal fluid
MH  - Cognition Disorders/*cerebrospinal fluid/genetics
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Peptide Fragments/cerebrospinal fluid
EDAT- 2008/03/13 09:00
MHDA- 2008/06/17 09:00
CRDT- 2008/03/13 09:00
PHST- 2008/03/13 09:00 [pubmed]
PHST- 2008/06/17 09:00 [medline]
PHST- 2008/03/13 09:00 [entrez]
AID - awn034 [pii]
AID - 10.1093/brain/awn034 [doi]
PST - ppublish
SO  - Brain. 2008 May;131(Pt 5):1252-8. doi: 10.1093/brain/awn034. Epub 2008 Mar 11.