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Open Access 25-09-2024 | Alzheimer's Disease | Original Communication

Contactin proteins in cerebrospinal fluid show different alterations in dementias

Authors: Besnik Muqaku, Sarah Anderl-Straub, Leonie Werner, Magdalena Nagl, Markus Otto, Charlotte E. Teunissen, Patrick Oeckl

Published in: Journal of Neurology

Abstract

Background

The proteins contactin (CNTN) 1–6 are synaptic proteins for which there is evidence that they are dysregulated in neurodegenerative dementias. Less is known about CNTN changes and differences in cerebrospinal fluid (CSF) of dementias, which can provide important information about alterations of the CNTN network and be of value for differential diagnosis.

Methods

We developed a mass spectrometry-based multiple reaction monitoring (MRM) method to simultaneously determine all six CNTNs in CSF samples using stable isotope-labeled standard peptides. The analytical performance of the method was evaluated for peptide stability, dilution linearity and precision. CNTNs were measured in 82 CSF samples from patients with Alzheimer’s disease (AD, n = 19), behavioural variant frontotemporal dementia (bvFTD, n = 18), Parkinson’s disease dementia/dementia with Lewy bodies (PDD/DLB, n = 18) and non-neurodegenerative controls (n = 27) and compared with core AD biomarkers.

Results

The MRM analysis revealed down-regulation of CNTN2 (fold change (FC) = 0.77), CNTN4 (FC = 0.75) and CNTN5 (FC = 0.67) in bvFTD and CNTN3 (FC = 0.72), CNTN4 (FC = 0.75) and CNTN5 (FC = 0.73) in PDD/DLB compared to AD. CNTN levels strongly correlated with each other in controls (r = 0.73), bvFTD (r = 0.86) and PDD/DLB (r = 0.70), but the correlation was significantly lower in AD (r = 0.41). CNTNs in AD did not show correlation even with core AD biomarkers. Combined use of CNTN1-6 levels increased diagnostic performance of AD core biomarkers.

Conclusions

Our data show CNTNs differentially altered in dementias and indicate CNTN homeostasis being selectively dysregulated in AD. The combined use of CNTNs with AD core biomarkers might help to improve differential diagnosis.

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Title: Contactin proteins in cerebrospinal fluid show different alterations in dementias
Authors: Besnik Muqaku
Sarah Anderl-Straub
Leonie Werner
Magdalena Nagl
Markus Otto
Charlotte E. Teunissen
Patrick Oeckl
Publication date: 25-09-2024
Publisher: Springer Berlin Heidelberg
Keywords: Alzheimer's Disease
Alzheimer's Disease
Dementia
Dementia
Biomarkers
Frontotemporal Dementia
Frontotemporal Dementia
Published in: Journal of Neurology
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-024-12694-6

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Contactin proteins in cerebrospinal fluid show different alterations in dementias

Abstract

Background

Methods

Results

Conclusions

Advances in Alzheimer's

Keynote webinar | Spotlight on modern management of frailty

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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Advances in Alzheimer's