BACKGROUND: We used 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 (Abeta) 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, 23 pM [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 Abeta(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 >or= 0.57, P <or= .009). CONCLUSION: Elevated BACE1 activity may contribute to the amyloidogenic process in sporadic AD and is associated with the intensity of axonal degeneration.
BACKGROUND: We used 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 (Abeta) 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, 23 pM [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 Abeta(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 >or= 0.57, P <or= .009). CONCLUSION: Elevated BACE1 activity may contribute to the amyloidogenic process in sporadic AD and is associated with the intensity of axonal degeneration.
Authors: Christopher J Holler; Robin L Webb; Ashley L Laux; Tina L Beckett; Dana M Niedowicz; Rachel R Ahmed; Yinxing Liu; Christopher R Simmons; Amy L S Dowling; Angela Spinelli; Moshe Khurgel; Steven Estus; Elizabeth Head; Louis B Hersh; M Paul Murphy Journal: Am J Pathol Date: 2011-11-07 Impact factor: 4.307
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Authors: Steven P Millard; Franziska Lutz; Ge Li; Douglas R Galasko; Martin R Farlow; Joseph F Quinn; Jeffrey A Kaye; James B Leverenz; Debby Tsuang; Chang-En Yu; Elaine R Peskind; Lynn M Bekris Journal: Neurobiol Aging Date: 2013-09-04 Impact factor: 4.673
Authors: Harald Hampel; Yong Shen; Dominic M Walsh; Paul Aisen; Les M Shaw; Henrik Zetterberg; John Q Trojanowski; Kaj Blennow Journal: Exp Neurol Date: 2009-10-06 Impact factor: 5.330