Nicotinamide as potential biomarker for Alzheimer’s disease: A translational study based on metabolomics
Standard
Nicotinamide as potential biomarker for Alzheimer’s disease: A translational study based on metabolomics. / Dalmasso, Maria Carolina; Arán, Martín; Galeano, Pablo; Perin, Silvina; Giavalisco, Patrick; Martino Adami, Pamela V; Novack, Gisela V.; Castaño, Eduardo M.; Cuello, A. Claudio; Scherer, Martin; Maier, Wolfgang; Wagner, Michael; Riedel-Heller, Steffi G; Ramirez, Alfredo; Morelli, Laura.
In: FRONT MOL BIOSCI, Vol. 9, 1067296, 2022, p. 1067296.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Nicotinamide as potential biomarker for Alzheimer’s disease: A translational study based on metabolomics
AU - Dalmasso, Maria Carolina
AU - Arán, Martín
AU - Galeano, Pablo
AU - Perin, Silvina
AU - Giavalisco, Patrick
AU - Martino Adami, Pamela V
AU - Novack, Gisela V.
AU - Castaño, Eduardo M.
AU - Cuello, A. Claudio
AU - Scherer, Martin
AU - Maier, Wolfgang
AU - Wagner, Michael
AU - Riedel-Heller, Steffi G
AU - Ramirez, Alfredo
AU - Morelli, Laura
PY - 2022
Y1 - 2022
N2 - Introduction: The metabolic routes altered in Alzheimer's disease (AD) brain are poorly understood. As the metabolic pathways are evolutionarily conserved, the metabolic profiles carried out in animal models of AD could be directly translated into human studies. Methods: We performed untargeted Nuclear Magnetic Resonance metabolomics in hippocampus of McGill-R-Thy1-APP transgenic (Tg) rats, a model of AD-like cerebral amyloidosis and the translational potential of these findings was assessed by targeted Gas Chromatography-Electron Impact-Mass Spectrometry in plasma of participants in the German longitudinal cohort AgeCoDe. Results: In rat hippocampus 26 metabolites were identified. Of these 26 metabolites, nine showed differences between rat genotypes that were nominally significant. Two of them presented partial least square-discriminant analysis (PLS-DA) loadings with the larger absolute weights and the highest Variable Importance in Projection (VIP) scores and were specifically assigned to nicotinamide adenine dinucleotide (NAD) and nicotinamide (Nam). NAD levels were significantly decreased in Tg rat brains as compared to controls. In agreement with these results, plasma of AD patients showed significantly reduced levels of Nam in respect to cognitively normal participants. In addition, high plasma levels of Nam showed a 27% risk reduction of progressing to AD dementia within the following 2.5 years, this hazard ratio is lost afterwards. Discussion: To our knowledge, this is the first report showing that a decrease of Nam plasma levels is observed couple of years before conversion to AD, thereby suggesting its potential use as biomarker for AD progression.
AB - Introduction: The metabolic routes altered in Alzheimer's disease (AD) brain are poorly understood. As the metabolic pathways are evolutionarily conserved, the metabolic profiles carried out in animal models of AD could be directly translated into human studies. Methods: We performed untargeted Nuclear Magnetic Resonance metabolomics in hippocampus of McGill-R-Thy1-APP transgenic (Tg) rats, a model of AD-like cerebral amyloidosis and the translational potential of these findings was assessed by targeted Gas Chromatography-Electron Impact-Mass Spectrometry in plasma of participants in the German longitudinal cohort AgeCoDe. Results: In rat hippocampus 26 metabolites were identified. Of these 26 metabolites, nine showed differences between rat genotypes that were nominally significant. Two of them presented partial least square-discriminant analysis (PLS-DA) loadings with the larger absolute weights and the highest Variable Importance in Projection (VIP) scores and were specifically assigned to nicotinamide adenine dinucleotide (NAD) and nicotinamide (Nam). NAD levels were significantly decreased in Tg rat brains as compared to controls. In agreement with these results, plasma of AD patients showed significantly reduced levels of Nam in respect to cognitively normal participants. In addition, high plasma levels of Nam showed a 27% risk reduction of progressing to AD dementia within the following 2.5 years, this hazard ratio is lost afterwards. Discussion: To our knowledge, this is the first report showing that a decrease of Nam plasma levels is observed couple of years before conversion to AD, thereby suggesting its potential use as biomarker for AD progression.
U2 - 10.3389/fmolb.2022.1067296
DO - 10.3389/fmolb.2022.1067296
M3 - SCORING: Journal article
VL - 9
SP - 1067296
JO - FRONT MOL BIOSCI
JF - FRONT MOL BIOSCI
SN - 2296-889X
M1 - 1067296
ER -
