BACKGROUND: Alzheimer Disease (AD) is the most common cause of dementia and it involves a high social and economic cost worldwide, and the health system still does not count with an effective treatment. This may be explained by the lack of a reliable early diagnosis and the complex physiological mechanisms involved in the disease development. In this sense, the cholinergic and serotonergic systems may be altered in the disease course. METHODS: In this study, metabolites from these pathways were determined in order to develop a non-invasive and early diagnosis model, as well as to advance in the knowledge of the physiopathological mechanisms of the disease. For this, plasma samples from mild cognitive impairment due to AD patients (MCI-AD, n = 25) and healthy controls (n = 25) were analysed. RESULTS: choline and tryptophan pathways were deregulated in MCI-AD. Therefore, a model based on betaine, cytidine, uridine, choline, acetylcholine, serotonin and tryptophan was developed, showing an AUC-ROC of 0.862, and sensitivity and specificity of 96% and 72%, respectively. CONCLUSION: Alterations in metabolites from these pathways are related to cognitive impairment and neurodegeneration, and they could be useful in AD diagnosis. Nevertheless, further research is required in order to validate this diagnosis model.
BACKGROUND:Alzheimer Disease (AD) is the most common cause of dementia and it involves a high social and economic cost worldwide, and the health system still does not count with an effective treatment. This may be explained by the lack of a reliable early diagnosis and the complex physiological mechanisms involved in the disease development. In this sense, the cholinergic and serotonergic systems may be altered in the disease course. METHODS: In this study, metabolites from these pathways were determined in order to develop a non-invasive and early diagnosis model, as well as to advance in the knowledge of the physiopathological mechanisms of the disease. For this, plasma samples from mild cognitive impairment due to ADpatients (MCI-AD, n = 25) and healthy controls (n = 25) were analysed. RESULTS:choline and tryptophan pathways were deregulated in MCI-AD. Therefore, a model based on betaine, cytidine, uridine, choline, acetylcholine, serotonin and tryptophan was developed, showing an AUC-ROC of 0.862, and sensitivity and specificity of 96% and 72%, respectively. CONCLUSION: Alterations in metabolites from these pathways are related to cognitive impairment and neurodegeneration, and they could be useful in AD diagnosis. Nevertheless, further research is required in order to validate this diagnosis model.
Authors: Susana López-Ortiz; Jose Pinto-Fraga; Pedro L Valenzuela; Juan Martín-Hernández; María M Seisdedos; Oscar García-López; Nicola Toschi; Francesca Di Giuliano; Francesco Garaci; Nicola Biagio Mercuri; Robert Nisticò; Enzo Emanuele; Simone Lista; Alejandro Lucia; Alejandro Santos-Lozano Journal: Int J Mol Sci Date: 2021-03-12 Impact factor: 5.923