Monoaminergic and Kynurenergic Characterization of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Cerebrospinal Fluid and Serum

Exploring the neurochemical continuum between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) with respect to monoamines and kynurenines in cerebrospinal fluid (CSF) and serum, may be useful to identify possible new research/therapeutic targets. Hence, we analysed monoamines and kynurenines in CSF and serum derived from patients with FTD (n = 39), ALS (n = 23), FTD-ALS (n = 4) and age-matched control subjects (n = 26), using reversed-phase ultra-high performance liquid chromatography (RP-UHPLC) with electrochemical detection (ECD) and liquid chromatography tandem mass spectrometry, respectively. We noted a shared dopaminergic disturbance in FTD and ALS when compared to CONTR, with significantly increased serum DA levels and decreased DOPAC concentrations, as well as decreased DOPAC/DA ratios in both disease groups. In CSF, significantly reduced DOPAC concentrations in FTD and ALS were observed as well. Here, a significant increase in DA levels and decrease in DOPAC/DA ratios was only found in FTD relative to CONTR. With respect to the kynurenine pathway (KP), we only found decreased HK/XA ratios, indicative for vitamin B6 status, in serum of ALS subjects compared to FTD. The dopaminergic commonalities observed in FTD and ALS might relate to a disturbance of dopaminergic nerve terminals in projection areas of the substantia nigra and/or ventral tegmental area, although these findings should first be confirmed in brain tissue. Lastly, based on the results of this work, the KP does not hold promise as a research/therapeutic target in FTD and ALS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11064-020-03002-5) contains supplementary material, which is available to authorized users.