PXD021918

PXD021918 is an original dataset announced via ProteomeXchange.

Title	Data 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.
Description	Alzheimer’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.
HostingRepository	PRIDE
AnnounceDate	2021-03-25
AnnouncementXML	Submission_2021-03-25_05:26:21.775.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Allan Stensballe
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-12 06:27:53	ID requested
1	2021-03-25 02:50:18	announced
⏵ 2	2021-03-25 05:26:22	announced	2021-03-25: Updated project metadata.

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]

submitter keyword: PASEF, AD,Proteomics, a-beta

Allan Stensballe
contact affiliation	Translational Biomarkers, Aalborg University, Denmark
contact email	as@hst.aau.dk
lab head
Allan Stensballe
contact affiliation	Aalborg University
contact email	as@hst.aau.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021918
     1. Label: PRIDE project
     2. Name: Data 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.