Skip to main content

01.12.2017 | Research | Ausgabe 1/2017 Open Access

Alzheimer's Research & Therapy 1/2017

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

Alzheimer's Research & Therapy > Ausgabe 1/2017
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13195-017-0245-y) contains supplementary material, which is available to authorized users.



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.


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.


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.


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.
Additional file 1: Figure S1. is showing cGMP and cAMP levels in CSF of subjects taking antidepressants compared with subjects not taking antidepressants separated into control and AD groups. A CSF cGMP levels were not altered in control subjects taking antidepressants compared with controls who did not take antidepressants (p = 0.79). B CSF cAMP levels were not altered in control subjects taking antidepressants compared with controls who did not take antidepressants (p = 0.51). C CSF cGMP levels were not altered in AD patients taking antidepressants compared with AD patients who did not take antidepressants (p = 0.60). D CSF cAMP levels were not altered in AD patients taking antidepressants compared with AD patients who did not take antidepressants (p = 0.38). Dark horizontal lines, mean of observed data; box, 25th and 75th percentiles; whiskers, 5th and 95th percentiles; dots, outliers. p values calculated using the Mann–Whitney rank-sum test. (TIF 514 kb)
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2017

Alzheimer's Research & Therapy 1/2017 Zur Ausgabe

Neu in den Fachgebieten Neurologie und Psychiatrie

Meistgelesene Bücher in der Neurologie & Psychiatrie

  • 2016 | Buch


    Das Lehrbuch vermittelt Ihnen das gesamte Neurologie-Prüfungswissen für Ihr Medizinstudium und bereitet auch junge Assistenzärzte durch detailliertes Fachwissen optimal auf die Praxis vor. Die komplett überarbeitete Auflage enthält sechs neue, interdisziplinäre Kapitel.

    Werner Hacke
  • 2016 | Buch

    Komplikationen in der Neurologie

    Das Buch schildert Ereignisse im Rahmen der Neuromedizin, die während der Diagnostik und Therapie neurologischer Erkrankungen und Symptome auftreten können. Die Fallbeispiele sensibilisieren Sie für mögliche Risikofaktoren, um das Auftreten solcher Komplikationen zu vermeiden.

    Frank Block
  • 2017 | Buch

    Facharztwissen Psychiatrie, Psychosomatik und Psychotherapie

    Leitsymptome, Untersuchungsmethoden, Krankheitsbilder, Notfälle & Co. – mit der Neuauflage des "Facharztwissens" sind Sie auf die Facharztprüfung in Psychiatrie und Psychotherapie optimal vorbereitet. In dieser 2. Auflage sind die Kapitel zu psychosomatischen Störungen deutlich ausgebaut.

    Prof. Dr. Dr. Frank Schneider
  • 2019 | Buch

    Kompendium der Psychotherapie

    Für Ärzte und Psychologen

    Dieses Werk wendet sich an Ärzte und Psychologen, die an psychiatrischen und psychosomatischen Kliniken oder an Psychotherapeutischen Ausbildungsinstituten arbeiten und in den vorhandenen Lehrbüchern der Psychotherapie den Brückenschlag zur …

    Tilo Kircher