Proteomics

Dataset Information

67

An integrated omics approach reveals synaptic plasticity changes in an APP/PS1 Alzheimer´s mouse model


ABSTRACT: Synaptic dysfunction occurs early in Alzheimer´s disease. However, efforts to protect against these detriments have not been possible due to the inadequate understanding of synaptic signalling pathways involved in the neuropathological disease process. The aim of this study was to elucidate the molecular mechanisms behind Alzheimer´s and synaptic plasticity-related signalling using a multi-omics and in situ imaging approach. We used an Alzheimer´s mouse model (APPswe/PSN1dE9, age of 12 month) (APP/PS1) and compared the changes on the proteome including global phosphorylation and N-linked glycosylation pattern, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched control mice in the neocortex, hippocampus, olfactory bulb and brainstem. Our analysis showed that signalling pathways related to synaptic functions associated to dendritic spine morphology, neurite outgrowth, long-term potentiaiton, CREB signalling and cytoskeletal dynamics were altered in the APP/PS1 transgenic mice, particular in the neocortex and olfactory bulb. This was associated with Aβ plaques and neurofibrillary tangle formation as well as microglial clustering in all brain regions except brainstem. The responses may be epigenetically modulated by the interaction with a number of miRNAs. We suggest that the alterations in synaptic plasticity-related signalling are associated to neurocognitive dysfunctions that resemble the situtation in human AD patients.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus musculus  

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Stefan J. Kempf  

LAB HEAD: Martin R. Larsen

PROVIDER: PXD003312 | Pride | 2016-05-11

REPOSITORIES: pride

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