PXD033566-1
PXD033566 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Tracking peripherally administered Amyloid-beta by stable isotope labeling-based proteomics |
| Description | Findings of early cerebral Amyloid-beta deposition in mice after peripheral injection of Amyloid-beta containing brain extracts, and humans following cadaveric human growth hormone treatment raised concerns that Amyloid-beta aggregates and possibly Alzheimer disease (AD) may be transmissible between individuals. Yet, proof that Amyloid-beta actually reaches the brain from the peripheral injection site is lacking. Here, we used a proteomic approach combining stable isotope labeling of mammals and untargeted and targeted mass spectrometry. Specifically, we generated 13C-isotope labeled brain extracts from mice expressing human Amyloid-beta and track 13C-Lys-labeled Amyloid-beta after intraperitoneal administration into young Amyloid betaPP transgenic mice. We detected injected Amyloid-beta in the liver and lymphoid tissues for up to 100 days. In contrast, injected 13C-Lys-labeled Amyloid-beta was not detectable in the brain whereas the mice incorporated 13C-Lys from the donor brain extracts into endogenous Amyloid-beta. Using a highly sensitive and specific proteomic approach, we demonstrated that Amyloid-beta does not reach the brain from the periphery. Our study argues against potential transmissibility of AD while opening new avenues to uncover mechanisms of pathophysiological protein deposition. Please note that corresponding MRM data for this project have been submitted elsewhere. |
| HostingRepository | MassIVE |
| AnnounceDate | 2022-05-27 |
| AnnouncementXML | Submission_2022-05-27_02:29:18.399.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Maciej Lalowski |
| SpeciesList | scientific name: Mus musculus; |
| ModificationList | 6x(13)C labeled L-lysine; Carbamidomethyl; Oxidation; Deamidated |
| Instrument | Exactive Plus; MALDI Synapt G2-S HDMS |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2022-04-29 11:34:27 | ID requested | |
| ⏵ 1 | 2022-05-27 02:29:18 | announced |
Publication List
| M. Brackhan, G. Calza, K.Lundgren, P. Bascuñana. T. Brüning, R. Soliymani, R. Kumar, A. Abelein, M. Baumann, M. Lalowski. J. Pahnke. Isotope-labeled amyloid-? does not transmit to the brain in a prion-like manner after peripheral administration. EMBO Reports (2022)e54405. doi.org/10.15252/embr.202154405. |
Keyword List
| submitter keyword: Alzheimer disease, APP-transgenic mice, brain, targeted and untargeted immuno-mass spectrometry, seeding |
Contact List
| Maciej Lalowski | |
|---|---|
| contact affiliation | Helsinki Institute for Life Science (HiLIFE) and Faculty of Medicine, Biochemistry/Developmental Biology, Meilahti Clinical Proteomics Core Facility, University of Helsinki, Helsinki, FI-00014 |
| contact email | maciej.lalowski@helsinki.fi |
| lab head | |
| Jens Pahnke | |
| contact affiliation | 1) Department of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway 2) LIED, University of Lubeck, 23538 Lubeck, Germany 3) Department of Pharmacology, Faculty of Medicine, University of Latvia, 1004 Riga, Latvia |
| contact email | jens.pahnke@gmail.com |
| lab head | |
| Mirjam Brackhan | |
| contact affiliation | 1) Department of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway 2) LIED, University of Lubeck, 23538 Lubeck, Germany |
| contact email | mirjam.brackhan@medisin.uio.no |
| lab head | |
| Maciej Lalowski | |
| contact affiliation | University of Helsinki/Medicum |
| contact email | maciej.lalowski@helsinki.fi |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000089339/ |
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