TY - JOUR
T1 - Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease
AU - Zetterberg, Henrik
AU - Andreasson, Ulf
AU - Hansson, Oskar
AU - Wu, Guoxin
AU - Sankaranarayanan, Sethu
AU - Andersson, Malin E.
AU - Buchhave, Peder
AU - Londos, Elisabet
AU - Umek, Robert M.
AU - Minthon, Lennart
AU - Simon, Adam J.
AU - Blennow, Kaj
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
M3 - Article
SN - 0003-9942
VL - 65
SP - 1102
EP - 1107
JO - Archives of Neurology
JF - Archives of Neurology
IS - 8
ER -