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European Archives of Psychiatry and Clinical Neuroscience

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12.11.2018 | Original Paper

Evaluation of the methoxy-X04 derivative BSC4090 for diagnosis of prodromal and early Alzheimer’s disease from bioptic olfactory mucosa

verfasst von: Hannah Pellkofer, Friedrich Ihler, Bernhard G. Weiss, Janina Trothe, Harindranath Kadavath, Monika Chongtham, Marcel Kunadt, Dietmar Riedel, Finn Lornsen, Petra Wilken, Claudia Bartels, Sina Hirschel, Sebastian G. Russo, Elke Stransky, Lutz Trojan, Boris Schmidt, Eckhardt Mandelkow, Markus Zweckstetter, Martin Canis, Anja Schneider

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 8/2019

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Abstract

Alzheimer’s disease (AD) pathology precedes the onset of clinical symptoms by several decades. Thus, biomarkers are required to identify prodromal disease stages to allow for the early and effective treatment. The methoxy-X04-derivative BSC4090 is a fluorescent ligand which was designed to target neurofibrillary tangles in AD. BSC4090 staining was previously detected in post-mortem brains and olfactory mucosa derived from AD patients. We tested BSC4090 as a potential diagnostic marker of prodromal and early AD using olfactory mucosa biopsies from 12 individuals with AD, 13 with mild cognitive impairment (MCI), and 10 cognitively normal (CN) controls. Receiver-operating curve analysis revealed areas under the curve of 0.78 for AD versus CN and of 0.86 for MCI due to AD versus MCI of other causes. BSC4090 labeling correlated significantly with cerebrospinal fluid levels of tau protein phosphorylated at T181. Using NMR spectroscopy, we find that BSC4090 binds to fibrillar and pre-fibrillar but not to monomeric tau. Thus, BSC4090 may be an interesting candidate to detect AD at the early disease stages.

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Titel: Evaluation of the methoxy-X04 derivative BSC4090 for diagnosis of prodromal and early Alzheimer’s disease from bioptic olfactory mucosa
verfasst von: Hannah Pellkofer
Friedrich Ihler
Bernhard G. Weiss
Janina Trothe
Harindranath Kadavath
Monika Chongtham
Marcel Kunadt
Dietmar Riedel
Finn Lornsen
Petra Wilken
Claudia Bartels
Sina Hirschel
Sebastian G. Russo
Elke Stransky
Lutz Trojan
Boris Schmidt
Eckhardt Mandelkow
Markus Zweckstetter
Martin Canis
Anja Schneider
Publikationsdatum: 12.11.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 8/2019
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-018-0955-6

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Evaluation of the methoxy-X04 derivative BSC4090 for diagnosis of prodromal and early Alzheimer’s disease from bioptic olfactory mucosa

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