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TTR is also present in cerebrospinal fluid where it can bind to A\u03b2-peptides and prevent A\u03b2 aggregation. We have previously shown that treatment of Alzheimer\u2019s Disease (AD) model mice with iododiflunisal (IDIF), a TTR tetramer stabilizing compound, prevents AD pathologies. This evidence positioned IDIF as a new lead drug for AD. In dissecting the mechanism of action of IDIF, we disclose here different labeling strategies for the preparation of <jats:sup>131<\/jats:sup>I-labeled IDIF and <jats:sup>131<\/jats:sup>I- and <jats:sup>124<\/jats:sup>I-labeled TTR, which have been further used for the preparation of IDIF-TTR complexes labeled either on the compound or the protein. The biodistribution of all labeled species after intravenous administration has been investigated in mice using <jats:italic>ex vivo<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> techniques. Our results confirm the capacity of TTR to cross the blood brain barrier (BBB) and suggest that the formation of TTR-IDIF complexes enhances BBB permeability of both IDIF and TTR. The increased TTR and IDIF brain concentrations may result in higher A\u03b2-peptide sequestration capacity with the subsequent inhibition of AD symptoms as we have previously observed in mice.<\/jats:p>","DOI":"10.1038\/s41598-019-50071-w","type":"journal-article","created":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T10:15:48Z","timestamp":1568974548000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Radiochemical examination of transthyretin (TTR) brain penetration assisted by iododiflunisal, a TTR tetramer stabilizer and a new candidate drug for AD"],"prefix":"10.1038","volume":"9","author":[{"given":"Xabier","family":"Rios","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3995-9596","authenticated-orcid":false,"given":"Vanessa","family":"G\u00f3mez-Vallejo","sequence":"additional","affiliation":[]},{"given":"Abraham","family":"Mart\u00edn","sequence":"additional","affiliation":[]},{"given":"Unai","family":"Coss\u00edo","sequence":"additional","affiliation":[]},{"given":"Miguel \u00c1ngel","family":"Morcillo","sequence":"additional","affiliation":[]},{"given":"Mobina","family":"Alemi","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2472-7055","authenticated-orcid":false,"given":"Isabel","family":"Cardoso","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7059-7418","authenticated-orcid":false,"given":"Jordi","family":"Quintana","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5421-8513","authenticated-orcid":false,"given":"Jes\u00fas","family":"Jim\u00e9nez-Barbero","sequence":"additional","affiliation":[]},{"given":"Ellen Y.","family":"Cotrina","sequence":"additional","affiliation":[]},{"given":"Gregorio","family":"Valencia","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7009-3738","authenticated-orcid":false,"given":"Gemma","family":"Arsequell","sequence":"additional","affiliation":[]},{"given":"Jordi","family":"Llop","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,9,20]]},"reference":[{"key":"50071_CR1","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.3233\/jad-170698","volume":"62","author":"JL Molinuevo","year":"2018","unstructured":"Molinuevo, J. 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