1 3 Eur Arch Psychiatry Clin Neurosci DOI 10.1007/s00406-017-0815-9 SHORT COMMUNICATION Plasma levels of soluble amyloid precursor protein β in symptomatic Alzheimer’s disease Panagiotis Alexopoulos 1,2 · Lena-Sophie Gleixner 1 · Lukas Werle 1,3 · Felix Buhl 1 · Nathalie Thierjung 1 · Evangelia Giourou 2 · Simone M. Kagerbauer 4 · Philippos Gourzis 2 · Hubert Kübler 5 · Timo Grimmer 1 · Igor Yakushev 6 · Jan Martin 4 · Alexander Kurz 1 · Robert Perneczky 7,8,9,10 Received: 7 November 2016 / Accepted: 6 June 2017 © Springer-Verlag GmbH Germany 2017 Keywords Soluble amyloid precursor protein β (sAPPβ) · Biomarker-underpinned diagnoses · FDG-PET · Upstream biomarkers · Mild cognitive impairment · Dementia due to Alzheimer’s disease Background Recently, a new biomarker-based conceptualization of Alz- heimer’s disease (AD) was proposed [1–6], enabling the identification of AD pathophysiology independently of its symptoms. The incorporation of biomarkers into the rou- tine diagnostic workup of symptomatic AD has been rec- ommended to increase diagnostic accuracy, since clinical diagnoses are not always confirmed at autopsy [7] or by the presence of the typical for AD biomarker profile [8–11]. In addition, biomarkers enable the estimation of the likelihood that symptoms are caused by AD pathophysiology [12, 13]. The term symptomatic AD refers not only to demen- tia but also to the less advanced stage of mild cognitive impairment (MCI) [13], which, in contrast to dementia, is Abstract The established biomarkers of Alzheimer’s disease (AD) require invasive endeavours or presuppose sophisticated technical equipment. Consequently, new bio- markers are needed. Here, we report that plasma levels of soluble amyloid precursor protein β (sAPPβ), a protein of the initial phase of the amyloid cascade, were significantly lower in patients with symptomatic AD (21 with mild cognitive impairment due to AD and 44 with AD demen- tia) with AD-typical cerebral hypometabolic pattern com- pared with 27 cognitively healthy elderly individuals with- out preclinical AD. These findings yield further evidence for the potential of sAPPβ in plasma as an AD biomarker candidate. Panagiotis Alexopoulos and Lena-Sophie Gleixner have contributed equally to this work. Electronic supplementary material The online version of this article (doi:10.1007/s00406-017-0815-9) contains supplementary material, which is available to authorized users. * Panagiotis Alexopoulos panos.alexopoulos@upatras.gr 1 Department of Psychiatry and Psychotherapy, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany 2 Department of Psychiatry, University Hospital of Rion, University of Patras, 26500 Patras, Greece 3 Max Planck Institute of Psychiatry, Munich, Germany 4 Department of Anaesthesiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany 5 Department of Urology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany 6 Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany 7 Department of Psychiatry and Psychotherapy, Ludwig- Maximilians-Universität München, Munich, Germany 8 Neuroepidemiology and Ageing Research Unit, Faculty of Medicine, School of Public Health, The Imperial College of Science, Technology and Medicine, London, UK 9 West London Mental Health NHS Trust, London, UK 10 German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany