Moderator of 1 Session
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CSF PROTEOME PROFILING REVEALS NOVEL BIOMARKERS FOR SPECIFIC DIAGNOSIS OF DEMENTIA WITH LEWY BODIES
Abstract
Aims
Specific diagnosis of dementia with Lewy bodies (DLB) remains challenging and biomarkers discriminating DLB from Alzheimer’s disease (AD) are highly needed. We aimed to identify the specific cerebrospinal fluid (CSF) proteomic changes that underlie DLB and identify translatable diagnostic biomarkers.
Methods
Proximity ligation-based multiplex immunoassays were used to measure 665 proteins in 534 CSF samples from patients with Dementia with Lewy bodies (n=109), AD-dementia (n=235) and cognitively-unimpaired controls (n=190).
Results
Nested linear models identified 97 CSF proteins dysregulated in DLB compared to controls (p<0.05). After comparison with the AD CSF proteome, we observed 52 of these proteins (54%) especially associated to DLB (e.g.DDC, GH, FCER2, MMP1), while 15 proteins (16%) showed opposite changes to those detected in AD patients (CRH, MMP3). The strongest dysregulated DLB protein was L-amino acid decarboxylase (DDC; >1.5 fold-change vs.CN or AD; q<1E-16), an enzyme involved in dopamine biosynthesis. DDC could optimally discriminate DLB from controls and AD patients (AUC: 0.91 and 0.81 respectively). Using penalized generalized linear modelling we identified a panel of 7-CSF markers including DDC that could discriminate DLB from AD patients with even higher accuracy (AUC: 0.93), which has been successfully translated into customized multiplex assays.
Conclusions
We unveil CSF changes specifically related to DLB pathophysiology and identified a panel of 7-CSF markers associated to specific aspects of DLB or AD pathophysiology able to discriminate these dementia types with high accuracy. Multiplex custom assays containing these markers are currently been clinically validated in independent cohorts for its potential use in diagnostic settings or clinical trials.