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Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease

Zetterberg, Henrik; Andreasson, Ulf; Hansson, Oskar LU ; Wu, Guoxin; Sankaranarayanan, Sethu; Andersson, Malin E.; Buchhave, Peder LU ; Londos, Elisabet LU ; Umek, Robert M. and Minthon, Lennart LU , et al. (2008) In Archives of Neurology 65(8). p.1102-1107
Abstract
Background: Weused a sensitive and specific beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) assay to determine the relationship between BACE1 activity in cerebrospinal fluid (CSF) and markers of APP metabolism and axonal degeneration in early and late stages of Alzheimer disease (AD). Objective: To assess CSF BACE1 activity in AD. Design: Case-control and longitudinal follow-up study. Setting: Specialized memory clinic. Patients: Eighty-seven subjects with AD, 33 cognitively normal control subjects, and 113 subjects with mild cognitive impairment (MCI), who were followed up for 3 to 6 years. Main Outcome Measures: Cerebrospinal fluid BACE1 activity in relation to diagnosis and CSF levels of secreted APP and amyloid beta... (More)
Background: Weused a sensitive and specific beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) assay to determine the relationship between BACE1 activity in cerebrospinal fluid (CSF) and markers of APP metabolism and axonal degeneration in early and late stages of Alzheimer disease (AD). Objective: To assess CSF BACE1 activity in AD. Design: Case-control and longitudinal follow-up study. Setting: Specialized memory clinic. Patients: Eighty-seven subjects with AD, 33 cognitively normal control subjects, and 113 subjects with mild cognitive impairment (MCI), who were followed up for 3 to 6 years. Main Outcome Measures: Cerebrospinal fluid BACE1 activity in relation to diagnosis and CSF levels of secreted APP and amyloid beta protein (A beta) isoforms and the axonal degeneration marker total tau. Results: Subjects with AD had higher CSF BACE1 activity (median, 30 pM [range, 11-96 pM]) than controls (median, 23pM [range, 8-43 pM]) (P=.02). Subjects with MCI who progressed to AD during the follow-up period had higher baseline BACE1 activity (median, 35 pM [range, 18-71 pM]) than subjects with MCI who remained stable (median, 29 pM [range, 14-83 pM]) (P < .001) and subjects with MCI who developed other forms of dementia (median, 20 pM [range, 10-56 pM]) (P <. 001). BACE1 activity correlated positively with CSF levels of secreted APP isoforms and A beta(40) in the AD and control groups and in all MCI subgroups (P <. 05) except the MCI subgroup that developed AD. Strong positive correlations were found between CSF BACE1 activity and total tau levels in all MCI subgroups (r >= 0.57, P <=. 009). Conclusion: Elevated BACE1 activity may contribute to the amyloidogenic process in sporadic AD and is associated with the intensity of axonal degeneration. (Less)
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Contribution to journal
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published
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Archives of Neurology
volume
65
issue
8
pages
1102 - 1107
publisher
American Medical Association
external identifiers
  • wos:000258377100012
  • scopus:49449108546
ISSN
0003-9942
language
English
LU publication?
yes
id
81990390-81b0-4eba-bea5-eb7978423ab7 (old id 1253519)
alternative location
http://archneur.ama-assn.org/cgi/content/abstract/65/8/1102
date added to LUP
2008-11-14 15:00:10
date last changed
2017-09-10 03:41:05
@article{81990390-81b0-4eba-bea5-eb7978423ab7,
  abstract     = {Background: Weused a sensitive and specific beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) assay to determine the relationship between BACE1 activity in cerebrospinal fluid (CSF) and markers of APP metabolism and axonal degeneration in early and late stages of Alzheimer disease (AD). Objective: To assess CSF BACE1 activity in AD. Design: Case-control and longitudinal follow-up study. Setting: Specialized memory clinic. Patients: Eighty-seven subjects with AD, 33 cognitively normal control subjects, and 113 subjects with mild cognitive impairment (MCI), who were followed up for 3 to 6 years. Main Outcome Measures: Cerebrospinal fluid BACE1 activity in relation to diagnosis and CSF levels of secreted APP and amyloid beta protein (A beta) isoforms and the axonal degeneration marker total tau. Results: Subjects with AD had higher CSF BACE1 activity (median, 30 pM [range, 11-96 pM]) than controls (median, 23pM [range, 8-43 pM]) (P=.02). Subjects with MCI who progressed to AD during the follow-up period had higher baseline BACE1 activity (median, 35 pM [range, 18-71 pM]) than subjects with MCI who remained stable (median, 29 pM [range, 14-83 pM]) (P &lt; .001) and subjects with MCI who developed other forms of dementia (median, 20 pM [range, 10-56 pM]) (P &lt;. 001). BACE1 activity correlated positively with CSF levels of secreted APP isoforms and A beta(40) in the AD and control groups and in all MCI subgroups (P &lt;. 05) except the MCI subgroup that developed AD. Strong positive correlations were found between CSF BACE1 activity and total tau levels in all MCI subgroups (r &gt;= 0.57, P &lt;=. 009). Conclusion: Elevated BACE1 activity may contribute to the amyloidogenic process in sporadic AD and is associated with the intensity of axonal degeneration.},
  author       = {Zetterberg, Henrik and Andreasson, Ulf and Hansson, Oskar and Wu, Guoxin and Sankaranarayanan, Sethu and Andersson, Malin E. and Buchhave, Peder and Londos, Elisabet and Umek, Robert M. and Minthon, Lennart and Simon, Adam J. and Blennow, Kaj},
  issn         = {0003-9942},
  language     = {eng},
  number       = {8},
  pages        = {1102--1107},
  publisher    = {American Medical Association},
  series       = {Archives of Neurology},
  title        = {Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease},
  volume       = {65},
  year         = {2008},
}