Fibrillar Aβ (beta) triggers microglial proteome alterations and dysfunction in Alzheimer mouse models

Monasor, Laura Sebastian; Müller, Stephan A.; Colombo, Alessio Vittorio; Tanrioever, Gaye; König, Jasmin; Roth, Stefan; Liesz, Arthur; Berghofer, Anna; Piechotta, Anke; Prestel, Matthias; Saito, Takashi; Saido, Takaomi C.; Herms, Jochen; Willem, Michael; Haass, Christian; Lichtenthaler, Stefan F. und Tahirovic, Sabina (2020): Fibrillar Aβ (beta) triggers microglial proteome alterations and dysfunction in Alzheimer mouse models. In: eLife, Bd. 9, e54083

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 and their functional consequences. Here, we performed an in-depth and time-resolved proteomic characterization of microglia in two mouse models of amyloid beta (A beta) pathology, the overexpression APPPS1 and the knock-in APP-NL-G-F (APP-KI) model. We identified a large panel of Microglial A beta Response Proteins (MARPs) that reflect heterogeneity of microglial alterations during early, middle and advanced stages of A beta deposition and occur earlier in the APPPS1 mice. Strikingly, the kinetic differences in proteomic profiles correlated with the presence of fibrillar A beta, rather than dystrophic neurites, suggesting that fibrillar A beta may trigger the AD-associated microglial phenotype and the observed functional decline. 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2050-084X
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198