Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid
Alberto Lleó(Hospital de Sant Pau), Raúl Núñez‐Llaves(Hospital de Sant Pau), Daniel Alcolea(Hospital de Sant Pau), Cristina Chiva(Universitat Pompeu Fabra), Daniel Balateu-Paños(Hospital de Sant Pau), Martí Colom‐Cadena(Hospital de Sant Pau), Gemma Gomez‐Giro(Hospital de Sant Pau), Laia Muñoz(Hospital de Sant Pau), Marta Querol‐Vilaseca(Hospital de Sant Pau), Jordi Pegueroles(Hospital de Sant Pau), Lorena Rami(Consorci Institut D'Investigacions Biomediques August Pi I Sunyer), Albert Lladó(Consorci Institut D'Investigacions Biomediques August Pi I Sunyer), José Luís Molinuevo(Consorci Institut D'Investigacions Biomediques August Pi I Sunyer), Mikel Tainta(Osakidetza), Jordi Clarimón(Hospital de Sant Pau), Tara L. Spires‐Jones(UK Dementia Research Institute), Rafael Blesa(Hospital de Sant Pau), Juan Fortea(Hospital de Sant Pau), Pablo Martínez‐Lage(Fundacion CITA Alzheimer), Raquel Sánchez‐Valle(Consorci Institut D'Investigacions Biomediques August Pi I Sunyer), Eduard Sabidó(Universitat Pompeu Fabra), Àlex Bayés(Universitat Autònoma de Barcelona), Olivia Belbin(Hospital de Sant Pau)
Cited by 252Open Access
Abstract
In the search for biomarkers of synapse loss associated with Alzheimer's disease (AD), we used shotgun proteomics to identify a panel of 9 synaptic proteins detectable in human cerebrospinal fluid (CSF). Expression at the human synapse was verified using super resolution microscopy. Using SRM, we monitored the panel in CSF from 3 independent clinical cohorts. We report 6 synaptic biomarkers that demonstrate changes in preclinical AD prior to markers of neurodegeneration, which could have clinical value for assessing disease progression.
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