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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2017

Open Access 01-12-2017 | Research

Reduced cGMP levels in CSF of AD patients correlate with severity of dementia and current depression

Authors: Raphael Hesse, Ludwig Lausser, Pauline Gummert, Florian Schmid, Anke Wahler, Cathrin Schnack, Katja S. Kroker, Markus Otto, Hayrettin Tumani, Hans A. Kestler, Holger Rosenbrock, Christine A. F. von Arnim

Published in: Alzheimer's Research & Therapy | Issue 1/2017

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Abstract

Background

Alzheimer’s disease (AD) is a neurodegenerative disorder, primarily affecting memory. That disorder is thought to be a consequence of neuronal network disturbances and synapse loss. Decline in cognitive function is associated with a high burden of neuropsychiatric symptoms (NPSs) such as depression. The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) are essential second messengers that play a crucial role in memory processing as well as synaptic plasticity and are potential therapeutic targets. Biomarkers that are able to monitor potential treatment effects and that reflect the underlying pathology are of crucial interest.

Methods

In this study, we measured cGMP and cAMP in cerebrospinal fluid (CSF) in a cohort of 133 subjects including 68 AD patients and 65 control subjects. To address the association with disease progression we correlated cognitive status with cyclic nucleotide levels. Because a high burden of NPSs is associated with decrease in cognitive function, we performed an exhaustive evaluation of AD-relevant marker combinations in a depressive subgroup.

Results

We show that cGMP, but not cAMP, levels in the CSF of AD patients are significantly reduced compared with the control group. Reduced cGMP levels in AD patients correlate with memory impairment based on Mini-Mental State Examination score (r = 0.17, p = 0.048) and tau as a marker of neurodegeneration (r = –0.28, p = 0.001). Moreover, we were able to show that AD patients suffering from current depression show reduced cGMP levels (p = 0.07) and exhibit a higher degree of cognitive impairment than non-depressed AD patients.

Conclusion

These results provide further evidence for an involvement of cGMP in AD pathogenesis and accompanying co-morbidities, and may contribute to elucidating synaptic plasticity alterations during disease progression.
Appendix
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Metadata
Title
Reduced cGMP levels in CSF of AD patients correlate with severity of dementia and current depression
Authors
Raphael Hesse
Ludwig Lausser
Pauline Gummert
Florian Schmid
Anke Wahler
Cathrin Schnack
Katja S. Kroker
Markus Otto
Hayrettin Tumani
Hans A. Kestler
Holger Rosenbrock
Christine A. F. von Arnim
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-017-0245-y

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