Panagiotis Alexopoulos1,2, Nathalie Thierjung2, Timo Grimmer2, Marion Ortner2, Polychronis Economou3, Konstantinos Assimakopoulos1, Philippos Gourzis1, Antonios Politis4,5, Robert Perneczky6,7,8,9. 1. Department of Psychiatry, University Hospital of Rion, University of Patras, Patras, Greece. 2. Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. 3. Department of Civil Engineering (Statistics), University of Patras, Patras, Greece. 4. First Department of Psychiatry, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece. 5. Department of Psychiatry, Division of Geriatric Psychiatry and Neuropsychiatry, John's Hopkins Medical School, Baltimore, Maryland, USA. 6. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany. 7. Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London, United Kingdom. 8. West London Mental Health NHS Trust, London, United Kingdom. 9. German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany.
Abstract
BACKGROUND/AIMS: The utility of β-site amyloid-β precursor protein (AβPP) cleaving enzyme 1 (BACE1) activity and soluble AβPP β (sAβPPβ) levels in cerebrospinal fluid (CSF) in detecting Alzheimer's disease (AD) is still elusive. METHODS: BACE1 activity and sAβPPβ concentration were measured in patients with AD dementia (n = 56) and mild cognitive impairment (MCI) due to AD (n = 76) with abnormal routine AD CSF markers, in patients with MCI with normal CSF markers (n = 39), and in controls without preclinical AD (n = 48). In a subsample with available 18F-fluorodeoxyglucose positron emission tomography (FDG PET) data, ordinal regression models were employed to compare the contribution of BACE1 and sAβPPβ to correct diagnostic classification to that of FDG PET. RESULTS: BACE1 activity was significantly higher in patients with MCI due to AD compared to both controls and patients with MCI with normal CSF markers. sAβPPβ did not differ between any of the studied groups. Interestingly, BACE1 activity was not found to be inferior to FDG PET as predictive covariate in differentiating between the diagnostic groups. CONCLUSIONS: Further studies using biomarker-underpinned diagnoses are warranted to shed more light on the potential diagnostic utility of BACE1 activity as AD biomarker candidate in MCI.
BACKGROUND/AIMS: The utility of β-site amyloid-β precursor protein (AβPP) cleaving enzyme 1 (BACE1) activity and soluble AβPP β (sAβPPβ) levels in cerebrospinal fluid (CSF) in detecting Alzheimer's disease (AD) is still elusive. METHODS:BACE1 activity and sAβPPβ concentration were measured in patients with AD dementia (n = 56) and mild cognitive impairment (MCI) due to AD (n = 76) with abnormal routine AD CSF markers, in patients with MCI with normal CSF markers (n = 39), and in controls without preclinical AD (n = 48). In a subsample with available 18F-fluorodeoxyglucose positron emission tomography (FDG PET) data, ordinal regression models were employed to compare the contribution of BACE1 and sAβPPβ to correct diagnostic classification to that of FDG PET. RESULTS:BACE1 activity was significantly higher in patients with MCI due to AD compared to both controls and patients with MCI with normal CSF markers. sAβPPβ did not differ between any of the studied groups. Interestingly, BACE1 activity was not found to be inferior to FDG PET as predictive covariate in differentiating between the diagnostic groups. CONCLUSIONS: Further studies using biomarker-underpinned diagnoses are warranted to shed more light on the potential diagnostic utility of BACE1 activity as AD biomarker candidate in MCI.
Authors: Inmaculada Lopez-Font; Claudia P Boix; Henrik Zetterberg; Kaj Blennow; Javier Sáez-Valero Journal: Mol Neurobiol Date: 2019-07-09 Impact factor: 5.590
Authors: Harald Hampel; Robert Vassar; Bart De Strooper; John Hardy; Michael Willem; Neeraj Singh; John Zhou; Riqiang Yan; Eugeen Vanmechelen; Ann De Vos; Robert Nisticò; Massimo Corbo; Bruno Pietro Imbimbo; Johannes Streffer; Iryna Voytyuk; Maarten Timmers; Amir Abbas Tahami Monfared; Michael Irizarry; Bruce Albala; Akihiko Koyama; Naoto Watanabe; Teiji Kimura; Lisa Yarenis; Simone Lista; Lynn Kramer; Andrea Vergallo Journal: Biol Psychiatry Date: 2020-02-13 Impact factor: 13.382