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1803_Ab_Native_CL_D_Anal_Chem.pdf (3.06 MB)

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2018-03-14

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/121061

Direct evidence of the presence of cross-linked Aβ dimers in the brains of Alzheimer's disease patients

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Recurs relacionat

http://dx.doi.org/10.1021/acs.analchem.7b04936

Resum

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.

Matèries

Malaltia d'Alzheimer, Marcadors bioquímics

Matèries (anglès)

Alzheimer's disease, Biochemical markers

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Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

VÁZQUEZ DE LA TORRE CERVERA, Aurelio, GAY I MARÍN, Marina, VILAPRINYÓ PASCUAL, Sílvia, MAZZUCATO, Roberta, SERRA BATISTE, Montserrat, VILASECA CASAS, Marta, CARULLA CASANOVAS, Natàlia. Direct evidence of the presence of cross-linked Aβ dimers in the brains of Alzheimer's disease patients. _Analytical Chemistry_. 2018. [consulta: 28 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/121061]

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