SIMOA Diagnostics on Alzheimer's Disease and Frontotemporal Dementia

Athanasia Chatziefstathiou; Sezgi Canaslan; Eirini Kanata; Kostas Vekrellis; Vasilios C Constantinides; George P Paraskevas; Elisabeth Kapaki; Matthias Schmitz; Inga Zerr; Konstantinos Xanthopoulos; Theodoros Sklaviadis; Dimitra Dafou

doi:10.3390/biomedicines12061253

SIMOA Diagnostics on Alzheimer's Disease and Frontotemporal Dementia

Biomedicines. 2024 Jun 4;12(6):1253. doi: 10.3390/biomedicines12061253.

Affiliations

¹ Department of Genetics, Development, and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
² Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University Medicine Göttingen, 37075 Göttingen, Germany.
³ Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
⁴ Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
⁵ Neurochemistry and Biological Markers Unit, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Eginition Hospital, 11528 Athens, Greece.
⁶ Second Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University General Hospital, 12462 Athens, Greece.

Abstract

Background: Accurate diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) represents a health issue due to the absence of disease traits. We assessed the performance of a SIMOA panel in cerebrospinal fluid (CSF) from 43 AD and 33 FTD patients with 60 matching Control subjects in combination with demographic-clinical characteristics.

Methods: 136 subjects (AD: n = 43, FTD: n = 33, Controls: n = 60) participated. Single-molecule array (SIMOA), glial fibrillary acidic protein (GFAP), neurofilament light (NfL), TAU, and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in CSF were analyzed with a multiplex neuro 4plex kit. Receiver operating characteristic (ROC) curve analysis compared area under the curve (AUC), while the principal of the sparse partial least squares discriminant analysis (sPLS-DA) was used with the intent to strengthen the identification of confident disease clusters.

Results: CSF exhibited increased levels of all SIMOA biomarkers in AD compared to Controls (AUCs: 0.71, 0.86, 0.92, and 0.94, respectively). Similar patterns were observed in FTD with NfL, TAU, and UCH-L1 (AUCs: 0.85, 0.72, and 0.91). sPLS-DA revealed two components explaining 19% and 9% of dataset variation.

Conclusions: CSF data provide high diagnostic accuracy among AD, FTD, and Control discrimination. Subgroups of demographic-clinical characteristics and biomarker concentration highlighted the potential of combining different kinds of data for successful and more efficient cohort clustering.

Keywords: AD; FTD; SIMOA platform; biomarkers; cerebrospinal fluid; dementias; multiplex; neurodegenerative diseases; sPLS-DA.

Grants and funding

The work was implemented in the framework of the Action RESEARCH–CREATE–INNOVATE co-funded by the European Regional Development Fund of the European Union and National Resources through the OP Competitiveness, Entrepreneurship, and Innovation (EPANEK) (grant number/project code: Τ1ΕDΚ-03884). The research work was supported by the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the 3rd Call for H.F.R.I. PhD Fellowships (Fellowship Number: 6325).