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

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.

• Authors: Yong Shen, Haibo Wang, Qiying Sun, Hailan Yao, Andrew P Keegan, Mike Mullan, Jeffrey Wilson, Simone Lista, Thomas Leyhe, Christoph Laske, Dan Rujescu, Allan Levey, Anders Wallin, Kaj Blennow, Rena Li, Harald Hampel
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 83 Issue 5 Pg. 447-455 (03 01 2018) ISSN: 1873-2402 [Electronic] United States
• PMID: 28359566 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Amyloid Precursor Protein Secretases
• Aspartic Acid Endopeptidases
• BACE1 protein, human

Topics

• Aged
• Alzheimer Disease (blood, diagnosis)
• Amyloid Precursor Protein Secretases (blood)
• Aspartic Acid Endopeptidases (blood)
• Biomarkers (blood)
• Cognitive Dysfunction (blood, diagnosis)
• Disease Progression
• Female
• Follow-Up Studies
• Humans
• Male
• Prodromal Symptoms
• Prognosis
• Sensitivity and Specificity