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)13195_2017_245_MOESM1_ESM.tif
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- Reduced cGMP levels in CSF of AD patients correlate with severity of dementia and current depression
Katja S. Kroker
Hans A. Kestler
Christine A. F. von Arnim
- BioMed Central