Frontotemporal dementia: Plasma metabolomic signature using gas chromatography–mass spectrometry

• Published in: Journal of pharmaceutical and biomedical analysis 2020-09, Vol.189, p.113424-113424, Article 113424
• Main Authors: Santos, Anna Luiza Morais, Vitório, Jessica Gardone, de Paiva, Maria José Nunes, Porto, Brenda Lee Simas, Guimarães, Henrique Cerqueira, Canuto, Gisele André Baptista, Carvalho, Maria das Graças, de Souza, Leonardo Cruz, de Toledo, Juliano Simões, Caramelli, Paulo, Duarte-Andrade, Filipe Fideles, Gomes, Karina Braga
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Frontotemporal dementia; Glutamatergic neurotransmission; Lipoperoxidation; Metabolomic
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2020.113424

•bvFTD group presented an impairment of amino acid metabolism compared to controls.•bvFTD patients showed changes in translation process compared to controls.•bvFTD group did not present different metabolites compared to AD group. Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive impairment in behavior, executive function, and language. The behavioral variant (bvFTD) is the most clinical common form and requires differential diagnosis with atypical Alzheimer’s disease (AD) cases. This study aimed to investigate the plasma metabolite profile of patients with bvFTD compared to AD patients and cognitively healthy individuals using gas chromatography coupled to mass spectrometry (GCMS). This study included nine patients with bvFTD, 17 with AD and 15 cognitively healthy controls (training set), whose data were validated on a testing set (eight bvFTD, 14 AD and ten controls). The metabolites were detected by GCMS. A tendency towards a reduction in the levels of palmitoleic, oleic and lauric acids was found in the bvFTD group compared to the AD group; however, no significance after multiple comparison correction was observed. However, bvFTD group showed reduced levels of creatinine, glycine, tryptophan, uric acid, hypoxanthine, serine, valine, threonine, isoleucine, homoserine, methionine, glutamic acid, capric acid, tartronic acid, fumaric acid, and myo-inositol, metabolites related to glycine/serine/threonine, alanine/aspartate/glutamate pathways and aminoacyl-tRNA biosynthesis, when compared to controls. The data suggest that bvFTD patients may present an impairment of amino acid metabolism and the translation process. This pioneering study on bvFTD and its plasma metabolomic signature can be useful to provide new ideas about pathophysiological mechanisms, as well as guide more robust studies in search of possible biomarkers for the diagnosis of this important dementia.