Towards a biomarker-based diagnosis of frontotemporal lobar degeneration

Date: 29 September 2017

Venue: Auditorium O3 (UAntwerp, Campus Drie Eiken, Building Q) - Universiteitsplein 1 - 2610 Wilrijk (Antwerp) (route: UAntwerpen, Campus Drie Eiken)

Time: 4:00 PM - 6:00 PM

PhD candidate: Joery Goossens

Principal investigator: Sebastiaan Engelborghs, Julie van der Zee

Short description: PhD defence Joery Goossens - Department of Biomedical Sciences



Abstract

In this thesis we examined the use of different biomarkers to improve the diagnosis of frontotemporal lobar degeneration (FTLD).

FTLD is a result of progressive atrophy of the frontal and temporal lobes of the brain, and is an important cause of early-onset dementia. There is extensive heterogeneity associated with FTLD, on both a clinical and a pathological level. Additionally, an overlap exists with other neurological disorders such as amyotrophic lateral sclerosis and Alzheimer’s disease (AD). As a result, making a reliable diagnosis of FTLD is difficult. The integration of biomarkers specific for FTLD pathology into the clinical diagnostic criteria is hypothesized to improve FTLD diagnosis.

One of the biomarkers we examined was electroencephalography (EEG). This topographical biomarker is expected to reflect the disruption of brain connectivity as a result of neurodegeneration. We defined a novel quantitative EEG measure that successfully differentiated between FTLD and AD.

Biomarkers that change in an even earlier phase of the disease, and are expected to be more specific for FTLD, are those reflecting the underlying pathological changes in the brain. For this purpose, different protein biomarkers were examined in cerebrospinal fluid (CSF). In a first study, the combination of several markers could be used to differentiate between FTLD, AD, and cognitively healthy controls. The most valuable protein was found to be neurofilament light chain, as it was specifically present in high concentrations in FTLD. A second study aimed at improving differential dementia diagnosis by investigating an innovative ELISA for the pathological protein tau. However, there was no added diagnostic value in comparison to already established biomarkers for AD. The other major pathological protein in FTLD, TDP-43, can so far not be reliably quantified in CSF. We investigated the sensitivity and specificity of antibodies used in current TDP-43 research, and report that there are additional issues to take into account when aiming to quantify TDP-43 in CSF.

Because of the heterogeneity associated with FTLD, it is likely necessary to combine different biomarkers into a diagnostic model. Such a model should at least include CSF levels of neurofilament light chain. Consequently, progress should still be made regarding the development and characterization of novel biomarkers, as well as the validation of existing ones.



Url: https://www.uantwerpen.be/en/faculties/fbd/research/public-defence-of-a-phd/