Dataset Information

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.

ABSTRACT: 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.

INSTRUMENT(S): maXis

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Rheumatoid Arthritis Disease Specific Synovial Fluid

DISEASE(S): Alzheimer's Disease

SUBMITTER: Allan Stensballe

LAB HEAD: Allan Stensballe

PROVIDER: PXD021918 | Pride | 2021-03-25

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	684281_IgG_1-1_1_GD11_01_2511.d.ZIP	Other
	684281_IgG_1-1_2_GD11_01_2584.d.ZIP	Other
	684281_IgG_1-2_1_GA8_01_2471.d.ZIP	Other
	684281_IgG_1-2_2_GA8_01_2547.d.ZIP	Other
	684281_IgG_1-3_1_GA9_01_2472.d.ZIP	Other

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Publications

Anti-Aβ Antibody Aducanumab Regulates the Proteome of Senile Plaques and Closely Surrounding Tissue in a Transgenic Mouse Model of Alzheimer's Disease.

Bastrup Joakim J Hansen Kathrine H KH Poulsen Thomas B G TBG Kastaniegaard Kenneth K Asuni Ayodeji A AA Christensen Søren S Belling Dorthe D Helboe Lone L Stensballe Allan A Volbracht Christiane C

Journal of Alzheimer's disease : JAD 20210101 1

<h4>Background</h4>Alzheimer's disease (AD) is characterized by accumulation of amyloid-β (Aβ) species and deposition of senile plaques (SPs). Clinical trials with the anti-Aβ antibody aducanumab have been completed recently.<h4>Objective</h4>To characterize the proteomic profile of SPs and surrounding tissue in a mouse model of AD in 10-month-old tgAPPPS1-21 mice after chronic treatment with aducanumab for four months with weekly dosing (10 mg/kg).<h4>Methods</h4>After observing significant red ...[more]

PMID: 33252074

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