PXD010356

PXD010356 is an original dataset announced via ProteomeXchange.

Title	Search for synaptic biomarkers of Alzheimer's disease
Description	s synapse degeneration is an early event in Alzheimer’s disease (AD) pathophysiology, a biofluid marker of synapse loss in living patients could be a surrogate marker of disease prognosis and therefore would be an excellent addition to the AD biomarker arsenal. With direct access to the brain interstitial fluid, the cerebrospinal fluid (CSF) is a potential source of synapse-derived proteins that could be potential biomarkers of underlying synapse degeneration. The aim of this study was to identify, verify and evaluate a set of synaptic proteins as surrogate CSF markers of underlying synapse loss in AD patients. In the Discovery Stage, we combined high-throughput shotgun proteomics of the CSF with an exhaustive search of the literature and public databases for proteomic studies of the CSF and synapse. A thorough characterization of the synaptic component of the CSF identified 210 synaptic proteins that are detectable in human CSF. We selected an initial panel of 22 candidate biomarkers for evaluation. In the Verification Stage, 12 proteins were discarded due to poor detection by targeted mass spectrometry (Selected Reaction Monitoring, SRM). We confirmed the expression of the remaining 10 proteins either directly at (Calsynytenin-1, GluR2, GluR4, Neurexins 2A and 3A, Neuroligin-2, Syntaxin-1B, Thy-1 and Vamp-2), or surrounding (Tenascin-R), the human synapse using Array Tomography microscopy and biochemical fractionation methods. We quantified the synaptic panel by SRM in CSF samples from 2 independent clinical cohorts of cognitively normal controls and all clinical stages of AD (n=140). A set of the panel proteins demonstrated a non-linear profile distinct to that of existing biomarkers whereby the CSF levels were decreased at the earliest preclinical stage of AD, reflecting reduced synaptic density in these asymptomatic individuals and elevated at later symptomatic stages when neurodegeneration is widespread. In conclusion, we have identified a set of novel synapse-specific proteins that could have clinical value for assessing disease progression in individuals at-risk for AD and potentially in other neurological disorders characterized by early synapse loss.
HostingRepository	PRIDE
AnnounceDate	2019-01-09
AnnouncementXML	Submission_2019-01-09_02:41:36.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Cristina Chiva
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-10 02:24:48	ID requested
⏵ 1	2019-01-09 02:41:37	announced

Lle, ó A, N, ú, ñ, ez-Llaves R, Alcolea D, Chiva C, Balateu-Pa, ñ, os D, Colom-Cadena M, Gomez-Giro G, Mu, ñ, oz L, Querol-Vilaseca M, Pegueroles J, Rami L, Llad, ó A, Molinuevo JL, Tainta M, Clarim, ó, n J, Spires-Jones T, Blesa R, Fortea J, Mart, í, nez-Lage P, S, á, nchez-Valle R, Sabid, ó E, Bay, é, s À, Belbin O, Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid. Mol Cell Proteomics, 18(3):546-560(2019) [pubmed]

ProteomeXchange project tag: Human Brain Proteome Project (HUPO_HBPP) (B/D-HPP)

curator keyword: Biomedical

submitter keyword: Alzheimer, biomarker, SRM, targeted

Eduard Sabido
contact affiliation	UPF/CRG Proteomics Unit
contact email	eduard.sabido@crg.eu
lab head
Cristina Chiva
contact affiliation	University Pompeu Fabra
contact email	cristina.chiva@upf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010356
     1. Label: PRIDE project
     2. Name: Search for synaptic biomarkers of Alzheimer's disease