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Biol Psychiatry. 2018 Mar 1;83(5):447-455. doi: 10.1016/j.biopsych.2017.02.007. Epub 2017 Mar 27.

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

Author information

1
Neurodegenerative Disorder Research Center and Brain Bank, Material Science at Microscale National Laboratory, School of Life Sciences, Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, University of Science and Technology of China, Hefei; Center for Advanced, Therapeutic Strategies for Brain Disorders, Sarasota; Department of Neurology, University of Florida College of Medicine, Gainesville, Florida.
2
Roskamp Institute, Sarasota.
3
Memory Center, Sarasota.
4
Department of Economics, Arizona State University, Tempe, Arizona.
5
Paris Institute of Translational Neurosciences IHU-A-ICM, Pitié-Salpêtrière University Hospital; AXA Research Fund & Université Pierre et Marie Curie Chair, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle.
6
Department of Psychiatry and Psychotherapy, University Hospital of Tübingen, Tübingen; Center of Old Age Psychiatry, Psychiatric University Hospital, Basel, Switzerland.
7
Department of Psychiatry and Psychotherapy, University Hospital of Tübingen, Tübingen.
8
Department of Psychiatry and Psychotherapy, Alzheimer Memorial Center, Ludwig-Maximilian University, Munich, Germany.
9
Department of Neurology and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, Georgia.
10
Department of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
11
Beijing Anding Hospital, Capital Medical University & Beijing Key Laboratory of Mental Disorders, Beijing; Beijing Institute for Brain Disorders, Beijing, China; Center for Hormone Advanced Science and Education, Sarasota. Electronic address: rli@rfdn.org.
12
Paris Institute of Translational Neurosciences IHU-A-ICM, Pitié-Salpêtrière University Hospital; AXA Research Fund & Université Pierre et Marie Curie Chair, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle; Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer, Hôpital Pitié-Salpêtrière, Paris, France.

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 (Vmax) 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.

KEYWORDS:

Alzheimer’s disease dementia; BACE1; Biomarker diagnosis; Mild cognitive impairment; Prediction; β-secretase

PMID:
28359566
PMCID:
PMC5656540
[Available on 2019-03-01]
DOI:
10.1016/j.biopsych.2017.02.007

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