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

Pellkofer, H., Ihler, F., Weiss, B. G., Trothe, J., Kadavath, H., Chongtham, M., et al. (2018). Evaluation of the methoxy-X04 derivative BSC4090 for diagnosis of prodromal and early Alzheimer's disease from bioptic olfactory mucosa. European Archives of Psychiatry and Clinical Neuroscience, (in press). doi:10.1007/s00406-018-0955-6.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-7DEE-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-AF68-4
Genre: Journal Article

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3008847.pdf (Preprint), 6MB
 
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Pellkofer, H., Author
Ihler, F., Author
Weiss, B. G., Author
Trothe, J., Author
Kadavath, H., Author
Chongtham, M., Author
Kunadt, M., Author
Riedel, D., Author
Lornsen, F., Author
Wilken, P., Author
Bartels, C., Author
Hirschel, S., Author
Russo, S. G., Author
Stransky, E., Author
Trojan, L., Author
Schmidt, B., Author
Mandelkow, E., Author
Zweckstetter, M.1, Author              
Canis, M., Author
Schneider, A., Author
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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Free keywords: Alzheimer’s disease; Biomarker; Tau; Olfactory epithelia; Methoxy-X04
 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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Language(s): eng - English
 Dates: 2018-11-12
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1007/s00406-018-0955-6
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Title: European Archives of Psychiatry and Clinical Neuroscience
Source Genre: Journal
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Pages: - Volume / Issue: - Sequence Number: (in press) Start / End Page: - Identifier: -