⮝ Full datasets listing

PXD021918

PXD021918 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleData in support of Anti-Aβ antibody treatment with Aducanumab modified the proteome of senile plaques and surrounding tissue and altered disease progression in a transgenic mouse model of Alzheimer’s disease.
DescriptionAlzheimer’s disease (AD) is the most comment type of dementia and is characterized by neuronal loss and cognitive decline. Aggregation and accumulation of Aβ proteoforms into senile plaques (SP) is one of the key hallmarks of the disease. The accumulation of Aβ in particular in hippocampus has been observed prior to cognitive decline, indicating a potential link between Aβ and the subsequent pathological events in AD. Several clinical trials have used immunotherapies targeting Aβ for degradation but have had diverging outcome in AD patients. We therefore set to determine the molecular profile of SP and surrounding tissue following biologics based immunotherapy using two antibodies, gantenerumab and aducanumab, that have high binding affinity to different Aβ epitopes for investigating the antibody Aβ-clearing properties. We used two cohorts of the APPPS1-21 PD mouse model that overexpresses human mutated APP (KM670/671NL) and PSEN1 (L166P). After chronic treatment for 4-month with weekly dose (20 and 10 mg/kg gantenerumab or aducanumab, respectively), we investigated SP load in two brain regions using thioflavin-S staining. A significant reduction of SP was observed in hippocampus of aducanumab treated mice while only a partial reduction was observed in same region of gantenerumab treated mice compared to respective control (irrelevant IgG and vehicle (PBS) treated mice). To determine the molecular changes associated with the aducanumab treatment, we applied two mass spectrometry (MS) methods, matrix-assisted laser desorption-ionization (MALDI) imaging, and microproteomics by combining laser microdissection and liquid chromatography-tandem MS (LC-MS/MS). We microdissected three subregions, containing SP, SP penumbra (SPP1), and an additional penumbra (SPP2) to the SPP1 extract from the hippocampus of the treated mice.
HostingRepositoryPRIDE
AnnounceDate2021-03-25
AnnouncementXMLSubmission_2021-03-25_05:26:21.775.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAllan Stensballe
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListiodoacetamide derivatized residue
InstrumentmaXis
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-10-12 06:27:53ID requested
12021-03-25 02:50:18announced
22021-03-25 05:26:22announced2021-03-25: Updated project metadata.
Publication List
10.3233/JAD-200715;
Bastrup J, Hansen KH, Poulsen TBG, Kastaniegaard K, Asuni AA, Christensen S, Belling D, Helboe L, Stensballe A, Volbracht C, Antibody Aducanumab Regulates the Proteome of Senile Plaques and Closely Surrounding Tissue in a Transgenic Mouse Model of Alzheimer's Disease. J Alzheimers Dis, 79(1):249-265(2021) [pubmed]
Keyword List
submitter keyword: PASEF, AD,Proteomics, a-beta
Contact List
Allan Stensballe
contact affiliationTranslational Biomarkers, Aalborg University, Denmark
contact emailas@hst.aau.dk
lab head
Allan Stensballe
contact affiliationAalborg University
contact emailas@hst.aau.dk
dataset submitter
Full Dataset Link List
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://ftp.pride.ebi.ac.uk/pride/data/archive/2021/03/PXD021918
PRIDE project URI
Repository Record List
[ + ]