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Herein, we aim to visualize \u03b1Syn inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. The fluorescent pyrimidoindole derivative THK\u2010565 probe was characterized by means of recombinant fibrils and brains from 10\u2010 to 11\u2010month\u2010old M83 mice. Concurrent wide\u2010field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed in vivo. Structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4\u2009T as well as scanning transmission x\u2010ray microscopy (STXM) were performed to characterize the iron deposits in the perfused brains. Immunofluorescence and Prussian blue staining were further performed on brain slices to validate the detection of \u03b1Syn inclusions and iron deposition. THK\u2010565 showed increased fluorescence upon binding to recombinant \u03b1Syn fibrils and \u03b1Syn inclusions in post\u2010mortem brain slices from patients with PD and M83 mice. Administration of THK\u2010565 in M83 mice showed higher cerebral retention at 20 and 40\u2009min post\u2010intravenous injection by wide\u2010field fluorescence compared to nontransgenic littermate mice, in congruence with the vMSOT findings. SWI\/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe<jats:sup>3+<\/jats:sup> form, as evinced by the STXM results. In conclusion, we demonstrated in vivo mapping of \u03b1Syn by means of noninvasive epifluorescence and vMSOT imaging and validated the results by targeting the THK\u2010565 label and SWI\/STXM identification of iron deposits in M83 mouse brains ex vivo.<\/jats:p>","DOI":"10.1111\/bpa.13288","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T05:25:01Z","timestamp":1720589101000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Visualizing alpha\u2010synuclein and iron deposition in <scp>M83<\/scp> mouse model of Parkinson's disease in vivo"],"prefix":"10.1111","volume":"34","author":[{"given":"Nadja","family":"Straumann","sequence":"first","affiliation":[{"name":"Institute for Regenerative Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin 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