Dataset Information

Microglial proteomic signatures in APPPS1 and APP-KI mice

ABSTRACT: Microglial dysfunction is a key pathological feature of Alzheimer´s disease (AD), but little is known about proteome-wide changes in microglia during the course of AD pathogenesis and their consequences for microglial function. Here, we performed an in-depth proteomic characterization of microglia in two AD mouse models, the overexpression APPPS1 and the knock-in AppNL-G-F (APP-KI) model. Proteome changes were followed from pre-deposition to early, middle and advanced stages of amyloid plaque pathology, revealing a large panel of Microglial Amyloid Response Proteins (MARPs) that reflect a heterogeneity of microglial alterations triggered by Adeposition. We demonstrate that the occurrence of MARPs coincided with the deposition of fibrillar A, recruitment of microglia to amyloid plaques and phagocytic dysfunction. While the proteomic and functional microglial changes were already markedly seen in 3 months old APPPS1 mice, they were delayed in the APP-KI model that generates substantially less fibrillar A. The identified microglial proteomic fingerprints of AD provide a valuable resource for functional studies of novel molecular targets and potential biomarkers for monitoring AD progression or therapeutic efficacy.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Microglial Cell

DISEASE(S): Alzheimer's Disease

SUBMITTER: Stephan Mueller

LAB HEAD: Stefan F. Lichtenthaler

PROVIDER: PXD016075 | Pride | 2020-06-09

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20181211_151646_APPPS1_APPPS1_DB.sne	Other
	20181211_161939_APPKI_APPPS1_DB.sne	Other
	APPPS1_ConditionSetup.xls	Xls
	APP_01M_1.raw	Raw
	APP_01M_2.raw	Raw

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Publications

Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models.

Sebastian Monasor Laura L Müller Stephan A SA Colombo Alessio Vittorio AV Tanrioever Gaye G König Jasmin J Roth Stefan S Liesz Arthur A Berghofer Anna A Piechotta Anke A Prestel Matthias M Saito Takashi T Saido Takaomi C TC Herms Jochen J Willem Michael M Haass Christian C Lichtenthaler Stefan F SF Tahirovic Sabina S

eLife 20200608

Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little is known about proteome-wide changes in microglia during the course of AD and their functional consequences. Here, we performed an in-depth and time-resolved proteomic characterization of microglia in two mouse models of amyloid β (Aβ) pathology, the overexpression APPPS1 and the knock-in APP-NL-G-F (APP-KI) model. We identified a large panel of Microglial Aβ Response Proteins (MARPs) that reflect hetero ...[more]

PMID: 32510331

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