Levels of β-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment

Zhenyu Zhong, Michael Ewers, Stefan Teipel, Katharina Bürger, Anders Wallin, Kaj Blennow, Ping He, Carrie McAllister, Harald Hampel, Yong Shen

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

Context: Elevated β-secretase (β-site amyloid precursor protein-cleaving enzyme1 [BACE1]) activity has been found in the brains of patients with sporadic Alzheimer disease (AD) compared with controls. Now we are particularly interested in whether BACE1 can be identified in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI), a population at high risk for AD. The possible presence of BACE1 in the CSF of patients with AD and MCI has so far gone unreported. Objective: To examine whether BACE1 can be identified in the CSF of patients with MCI. Design: We evaluated CSF BACE1 levels using 2 sandwich enzyme-linked immunosorbent assays, BACE1 enzymatic activities by means of synthetic fluorescence substrate, and total amyloid-β peptide levels using a sandwich enzyme-linked immunosorbent assay. Setting: Two independent research centers. Participants: Eighty patients with sporadic AD, 59 patients with MCI, and 69 controls. Main Outcome Measures: BACE1 levels and enzymatic activities and amyloid-β peptide levels. Results: Increased CSF levels of BACE1 protein were associated with increased risk ratios (RRs) for patients with MCI compared with controls (RR, 2.08; 95% confidence interval [CI], 1.58-2.58) and patients with AD (RR, 1.65; 95% CI, 1.19-2.03). Similarly, patients with MCI showed increased levels of BACE1 activity compared with controls (RR, 2.17; 95% CI, 1.66-2.71) and patients with AD (RR, 3.71; 95% CI, 2.74-4.36). For total amyloid-β peptide and tau, increased CSF levels were associated with a higher risk of MCI compared with controls. The BACE1 activity was significantly correlated with BACE1 protein level (ρ=0.23; P

Original languageEnglish (US)
Pages (from-to)718-726
Number of pages9
JournalArchives of General Psychiatry
Volume64
Issue number6
DOIs
StatePublished - Jun 2007
Externally publishedYes

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Amyloid Precursor Protein Secretases
Cerebrospinal Fluid
Alzheimer Disease
Odds Ratio
Amyloid
Confidence Intervals
Peptides
Enzyme-Linked Immunosorbent Assay
Cognitive Dysfunction
Proteins
Fluorescence
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Psychiatry and Mental health

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Levels of β-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment. / Zhong, Zhenyu; Ewers, Michael; Teipel, Stefan; Bürger, Katharina; Wallin, Anders; Blennow, Kaj; He, Ping; McAllister, Carrie; Hampel, Harald; Shen, Yong.

In: Archives of General Psychiatry, Vol. 64, No. 6, 06.2007, p. 718-726.

Research output: Contribution to journalArticle

Zhong, Z, Ewers, M, Teipel, S, Bürger, K, Wallin, A, Blennow, K, He, P, McAllister, C, Hampel, H & Shen, Y 2007, 'Levels of β-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment', Archives of General Psychiatry, vol. 64, no. 6, pp. 718-726. https://doi.org/10.1001/archpsyc.64.6.718
Zhong, Zhenyu ; Ewers, Michael ; Teipel, Stefan ; Bürger, Katharina ; Wallin, Anders ; Blennow, Kaj ; He, Ping ; McAllister, Carrie ; Hampel, Harald ; Shen, Yong. / Levels of β-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment. In: Archives of General Psychiatry. 2007 ; Vol. 64, No. 6. pp. 718-726.
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abstract = "Context: Elevated β-secretase (β-site amyloid precursor protein-cleaving enzyme1 [BACE1]) activity has been found in the brains of patients with sporadic Alzheimer disease (AD) compared with controls. Now we are particularly interested in whether BACE1 can be identified in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI), a population at high risk for AD. The possible presence of BACE1 in the CSF of patients with AD and MCI has so far gone unreported. Objective: To examine whether BACE1 can be identified in the CSF of patients with MCI. Design: We evaluated CSF BACE1 levels using 2 sandwich enzyme-linked immunosorbent assays, BACE1 enzymatic activities by means of synthetic fluorescence substrate, and total amyloid-β peptide levels using a sandwich enzyme-linked immunosorbent assay. Setting: Two independent research centers. Participants: Eighty patients with sporadic AD, 59 patients with MCI, and 69 controls. Main Outcome Measures: BACE1 levels and enzymatic activities and amyloid-β peptide levels. Results: Increased CSF levels of BACE1 protein were associated with increased risk ratios (RRs) for patients with MCI compared with controls (RR, 2.08; 95{\%} confidence interval [CI], 1.58-2.58) and patients with AD (RR, 1.65; 95{\%} CI, 1.19-2.03). Similarly, patients with MCI showed increased levels of BACE1 activity compared with controls (RR, 2.17; 95{\%} CI, 1.66-2.71) and patients with AD (RR, 3.71; 95{\%} CI, 2.74-4.36). For total amyloid-β peptide and tau, increased CSF levels were associated with a higher risk of MCI compared with controls. The BACE1 activity was significantly correlated with BACE1 protein level (ρ=0.23; P",
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T1 - Levels of β-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment

AU - Zhong, Zhenyu

AU - Ewers, Michael

AU - Teipel, Stefan

AU - Bürger, Katharina

AU - Wallin, Anders

AU - Blennow, Kaj

AU - He, Ping

AU - McAllister, Carrie

AU - Hampel, Harald

AU - Shen, Yong

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N2 - Context: Elevated β-secretase (β-site amyloid precursor protein-cleaving enzyme1 [BACE1]) activity has been found in the brains of patients with sporadic Alzheimer disease (AD) compared with controls. Now we are particularly interested in whether BACE1 can be identified in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI), a population at high risk for AD. The possible presence of BACE1 in the CSF of patients with AD and MCI has so far gone unreported. Objective: To examine whether BACE1 can be identified in the CSF of patients with MCI. Design: We evaluated CSF BACE1 levels using 2 sandwich enzyme-linked immunosorbent assays, BACE1 enzymatic activities by means of synthetic fluorescence substrate, and total amyloid-β peptide levels using a sandwich enzyme-linked immunosorbent assay. Setting: Two independent research centers. Participants: Eighty patients with sporadic AD, 59 patients with MCI, and 69 controls. Main Outcome Measures: BACE1 levels and enzymatic activities and amyloid-β peptide levels. Results: Increased CSF levels of BACE1 protein were associated with increased risk ratios (RRs) for patients with MCI compared with controls (RR, 2.08; 95% confidence interval [CI], 1.58-2.58) and patients with AD (RR, 1.65; 95% CI, 1.19-2.03). Similarly, patients with MCI showed increased levels of BACE1 activity compared with controls (RR, 2.17; 95% CI, 1.66-2.71) and patients with AD (RR, 3.71; 95% CI, 2.74-4.36). For total amyloid-β peptide and tau, increased CSF levels were associated with a higher risk of MCI compared with controls. The BACE1 activity was significantly correlated with BACE1 protein level (ρ=0.23; P

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