2026-04-13T13:32:20Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1210612025-12-04T19:31:19Zcom_2072_1057col_2072_478908col_2072_478917

00925njm 22002777a 4500 dc Vázquez de la Torre Cervera, Aurelio author Gay i Marín, Marina author Vilaprinyó Pascual, Sílvia author Mazzucato, Roberta author Serra Batiste, Montserrat author Vilaseca Casas, Marta author Carulla Casanovas, Natàlia author 2018-03-23T11:21:16Z 2019-03-14T06:10:21Z 2018-03-14 2018-03-20T11:59:58Z Brain-derived amyloid-β (Aβ) dimers are associated with Alzheimer´s disease (AD). However, their covalent nature remains controversial. This feature is relevant, as a covalent cross-link would make brain-derived dimers (brain dimers) more synaptotoxic than Aβ monomers and would make them suitable candidates for biomarker development. To resolve this controversy, we here present a three-step approach. First, we validated a type of synthetic cross-linked Aβ (CL Aβ) dimers, obtained by means of the photo-induced cross-linking of unmodified proteins (PICUP) reaction, as well-defined mimics of putative brain CL Aβ dimers. Second, we used these PICUP CL Aβ dimers as standards to improve the isolation of brain Aβ dimers and to develop state-of-the-art mass spectrometry (MS) strategies to allow their characterization. Third, we applied these MS methods to the analysis of brain Aβ dimer samples allowing the detection of the CL [Aβ(6-16)]2 peptide comprising a dityrosine cross-link. This result demonstrates the presence of CL Aβ dimers in the brains of patients with AD and opens up avenues for establishing new therapeutic targets and developing novel biomarkers for this disease. Malaltia d'Alzheimer Marcadors bioquímics Alzheimer's disease Biochemical markers Direct evidence of the presence of cross-linked Aβ dimers in the brains of Alzheimer's disease patients