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- W2896561179 abstract "Alzheimer's disease (AD) is characterised by early and profound synapse loss. Consequently, an in vivo marker of synapse degeneration would be an excellent addition to the AD biomarker arsenal. The synaptic component of the cerebrospinal fluid (CSF) was characterised by combining high-throughput discovery proteomics with an exhaustive search of the literature and public databases. Evaluation of synapse-specific expression of the panel proteins was achieved by combining quantification in synapse-enriched cortical tissue fractions and array tomography microscopy. The synaptic panel was quantified in CSF samples from 2 independent clinical cohorts (n=140) comprising cognitively healthy controls and all AD clinical and preclinical stages using selected reaction monitoring mass spectrometry. We identified 180 synaptic proteins detectable in the CSF. A panel of 10 synaptic proteins was selected for evaluation. Expression of the synaptic proteins to the human cortical synapse either directly at, or in synapse-associated structures was confirmed for panel proteins. In the CSF, a subset of synaptic proteins were decreased 0.8-fold in subjects at preclinical AD stage 1, before neurodegeneration is widespread (p<0.04). All panel proteins were increased 1.2 to 1.4-fold at the symptomatic stages (p<0.05). Since the CSF profile of synaptic proteins may be confounded at least in part by underlying neurodegeneration, we report a ratio of synaptic proteins to the axonal degeneration marker, neurofilament-light (Nf-L) that could be further informative in subjects with widespread neurodegeneration. We report a non-linear CSF profile for synaptic proteins that is distinct to that of established AD biomarkers. We propose that a set of synaptic proteins can be informative of the underlying synapse loss in AD, particularly at preclinical stages before neuronal loss becomes widespread." @default.
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- W2896561179 date "2018-07-01" @default.
- W2896561179 modified "2023-10-18" @default.
- W2896561179 title "P2‐262: A CEREBROSPINAL FLUID PANEL OF SYNAPTIC PROTEINS ACROSS THE ENTIRE ALZHEIMER'S DISEASE CONTINUUM" @default.
- W2896561179 doi "https://doi.org/10.1016/j.jalz.2018.06.951" @default.
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