San Pablo CEU University
Pharmacy
Dr. del Campo’s main scientific interest is to understand the biological changes that underlie the different dementia types and translate this knowledge into applicable diagnostic tests and potential therapeutic targets. As translational neurobiologist, she has worked with human samples as well as different cell and animal models. She is currently co-leading highly collaborative studies analysing the proteome in different biofluids (CSF and plasma) from patients with different types of dementia (PRIDE and bPRIDE projects) to identify early and specific biomarker signatures that might be useful in clinical setting and trials. Understanding the molecular mechanisms behind those changes is also highly relevant, as it may reveal potential therapeutic targets. By combining -omics data (e.g. proteome and genome), she aims also to identify novel pathways and molecules involved in the pathogenesis of dementia.

Moderator of 1 Session

Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
09:10 AM - 11:10 AM
Room
ONSITE: 131-132

Presenter of 1 Presentation

CSF PROTEOME PROFILING REVEALS NOVEL BIOMARKERS FOR SPECIFIC DIAGNOSIS OF DEMENTIA WITH LEWY BODIES

Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
09:10 AM - 11:10 AM
Room
ONSITE: 131-132
Lecture Time
10:25 AM - 10:40 AM

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.

Hide