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Author Notes:

Corresponding author: Dr. Rena Li, Beijing Anding Hospital, Capital Medical University, Beijing, China 100088 rli@rfdn.org

We would like to thank Dr. Michael Ewers from Ludwig-Maximilian University, Munich, Germany, for the critical discussion of the study concept.

We would also like to thank Juliet Shen for her English editing services.

The authors report no biomedical financial interests or potential conflicts of interest.

Subjects:

Research Funding:

This work was supported by the National Key Research and Development Program, Ministry of Science and Technology of China 2016YFC1300500-03 (YS), the National Institute on Aging (NIHR01AG032441-01, YS, NIHR21 AG049237, RL and RO1AG025888, YS); Alzheimer’s Association (Zenith Award and IIRG-07-59510, YS); the American Health Assistance Foundation (G2006-118, RL); HH is supported by the AXA Research Fund, the Fondation Université Pierre et Marie Curie and the Fondation pour la Recherche sur Alzheimer, Paris, France. Ce travail a beneficie d’une aide de l’Etat «Investissements d’avenir » ANR-10-IAIHU-06 (HH).

The research leading to these results has received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6) (HH).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Psychiatry
  • Neurosciences & Neurology
  • Alzheimer's disease dementia
  • BACE1
  • beta-secretase
  • Biomarker diagnosis
  • Mild cognitive impairment
  • Prediction
  • AMYLOID PRECURSOR PROTEIN
  • CEREBROSPINAL-FLUID
  • PUNCTURE HEADACHE
  • BACE1 ACTIVITY
  • BIOMARKERS
  • INHIBITORS
  • EXPRESSION
  • REDUCTION
  • MUTATION
  • DESIGN

Increased Plasma Beta-Secretase 1 May Predict Conversion to Alzheimer's Disease Dementia in Individuals With Mild Cognitive Impairment

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Journal Title:

Biological Psychiatry

Volume:

Volume 83, Number 5

Publisher:

, Pages 447-455

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background: Increased beta-secretase 1 (BACE1) activity has consistently been detected in brain tissue and cerebrospinal fluid of subjects with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) compared with control subjects. The collection of cerebrospinal fluid by lumbar puncture is invasive. We sought to identify the presence of plasma BACE1 activity and determine potential alterations in subjects with MCI with clinical follow-up examinations for 3 years using patients with diagnosed probable AD dementia compared with healthy control subjects. Methods: Seventy-five patients with probable AD, 96 individuals with MCI, and 53 age-matched and sex-matched healthy control subjects were recruited from three independent international academic memory clinics and AD research expert centers. Plasma BACE1 activity was measured by a synthetic fluorescence substrate enzyme-linked immunosorbent assay. BACE1 protein expression was assessed by Western blotting using three different antibodies that recognize the epitopes of the N-terminus, C-terminus, and full-length BACE1. Results: Compared with healthy control subjects, plasma BACE1 activity (V max ) significantly increased by 53.2% in subjects with MCI and by 68.9% in patients with probable AD. Subjects with MCI who converted to probable AD dementia at follow-up examinations exhibited significantly higher BACE1 activity compared with cognitively stable MCI nonconverters and showed higher levels of BACE1 activity than patients with AD. Conclusions: Plasma BACE1 activity is significantly increased in MCI converters and patients with probable AD. The sensitivities and specificities of BACE1 activity for the patients were 84% and 88%, respectively. Our results indicate that plasma BACE1 activity may be a biomarker for AD risk and could predict progression from prodromal to probable AD dementia.

Copyright information:

© 2017 Society of Biological Psychiatry

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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