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Decreased levels of cGMP in CSF are associated with cognitive decline and amyloid pathology in Alzheimer ’ s disease 1 Authors :

Aims: Levels or the cyclic nucleotides cGMP or cAMP that play important roles in memory processes are not characterized in Alzheimer ́s disease (AD). The aim of this study was to analyze the levels of these nucleotides in cerebrospinal fluid (CSF) samples from patients diagnosed with clinical and prodromal stages of AD and study the expression level of the enzymes that hydrolized them (phosphodiesterases: PDEs) in the brain of AD patients vs controls. Methods: For cGMP and cAMP CSF analysis the cohort (n=79) included cognitively normal participants (SCI), individuals with mild cognitive impairment stable or AD converters (sMCI and cMCI) and mild AD patients. A high throughput liquid chromatography–mass spectrometry method (LC-MS/MS) was used. Interactions between CSF cGMP or cAMP with MMSE score, CSF Aβ(1-42), and CSF p-tau were analyzed. For PDE4, 5, 9 and 10 expression analysis, brains of AD patients vs controls (n=7 and n=8) were used. A cc ep te d A rti cl e