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Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study

Hyperhomocysteinemia has been suggested potentially to contribute to a variety of pathologies, such as Alzheimer’s disease (AD). While the impact of hyperhomocysteinemia on AD has been investigated extensively, there are scarce data on the effect of AD on hyperhomocysteinemia. The aim of this in viv...

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Autores principales: Nieraad, Hendrik, de Bruin, Natasja, Arne, Olga, Hofmann, Martine C. J., Gurke, Robert, Schmidt, Dominik, Ritter, Marcel, Parnham, Michael J., Geisslinger, Gerd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831937/
https://www.ncbi.nlm.nih.gov/pubmed/33477684
http://dx.doi.org/10.3390/ijms22020927
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author Nieraad, Hendrik
de Bruin, Natasja
Arne, Olga
Hofmann, Martine C. J.
Gurke, Robert
Schmidt, Dominik
Ritter, Marcel
Parnham, Michael J.
Geisslinger, Gerd
author_facet Nieraad, Hendrik
de Bruin, Natasja
Arne, Olga
Hofmann, Martine C. J.
Gurke, Robert
Schmidt, Dominik
Ritter, Marcel
Parnham, Michael J.
Geisslinger, Gerd
author_sort Nieraad, Hendrik
collection PubMed
description Hyperhomocysteinemia has been suggested potentially to contribute to a variety of pathologies, such as Alzheimer’s disease (AD). While the impact of hyperhomocysteinemia on AD has been investigated extensively, there are scarce data on the effect of AD on hyperhomocysteinemia. The aim of this in vivo study was to investigate the kinetics of homocysteine (HCys) and homocysteic acid (HCA) and effects of AD-like pathology on the endogenous levels. The mice received a B-vitamin deficient diet for eight weeks, followed by the return to a balanced control diet for another eight weeks. Serum, urine, and brain tissues of App(NL-G-F) knock-in and C57BL/6J wild type mice were analyzed for HCys and HCA using LC-MS/MS methods. Hyperhomocysteinemic levels were found in wild type and knock-in mice due to the consumption of the deficient diet for eight weeks, followed by a rapid normalization of the levels after the return to control chow. Hyperhomocysteinemic App(NL-G-F) mice had significantly higher HCys in all matrices, but not HCA, compared to wild type control. Higher serum concentrations were associated with elevated levels in both the brain and in urine. Our findings confirm a significant impact of AD-like pathology on hyperhomocysteinemia in the App(NL-G-F) mouse model. The immediate normalization of HCys and HCA after the supply of B-vitamins strengthens the idea of a B-vitamin intervention as a potentially preventive treatment option for HCys-related disorders such as AD.
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spelling pubmed-78319372021-01-26 Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study Nieraad, Hendrik de Bruin, Natasja Arne, Olga Hofmann, Martine C. J. Gurke, Robert Schmidt, Dominik Ritter, Marcel Parnham, Michael J. Geisslinger, Gerd Int J Mol Sci Article Hyperhomocysteinemia has been suggested potentially to contribute to a variety of pathologies, such as Alzheimer’s disease (AD). While the impact of hyperhomocysteinemia on AD has been investigated extensively, there are scarce data on the effect of AD on hyperhomocysteinemia. The aim of this in vivo study was to investigate the kinetics of homocysteine (HCys) and homocysteic acid (HCA) and effects of AD-like pathology on the endogenous levels. The mice received a B-vitamin deficient diet for eight weeks, followed by the return to a balanced control diet for another eight weeks. Serum, urine, and brain tissues of App(NL-G-F) knock-in and C57BL/6J wild type mice were analyzed for HCys and HCA using LC-MS/MS methods. Hyperhomocysteinemic levels were found in wild type and knock-in mice due to the consumption of the deficient diet for eight weeks, followed by a rapid normalization of the levels after the return to control chow. Hyperhomocysteinemic App(NL-G-F) mice had significantly higher HCys in all matrices, but not HCA, compared to wild type control. Higher serum concentrations were associated with elevated levels in both the brain and in urine. Our findings confirm a significant impact of AD-like pathology on hyperhomocysteinemia in the App(NL-G-F) mouse model. The immediate normalization of HCys and HCA after the supply of B-vitamins strengthens the idea of a B-vitamin intervention as a potentially preventive treatment option for HCys-related disorders such as AD. MDPI 2021-01-18 /pmc/articles/PMC7831937/ /pubmed/33477684 http://dx.doi.org/10.3390/ijms22020927 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nieraad, Hendrik
de Bruin, Natasja
Arne, Olga
Hofmann, Martine C. J.
Gurke, Robert
Schmidt, Dominik
Ritter, Marcel
Parnham, Michael J.
Geisslinger, Gerd
Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study
title Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study
title_full Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study
title_fullStr Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study
title_full_unstemmed Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study
title_short Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study
title_sort effects of alzheimer-like pathology on homocysteine and homocysteic acid levels—an exploratory in vivo kinetic study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831937/
https://www.ncbi.nlm.nih.gov/pubmed/33477684
http://dx.doi.org/10.3390/ijms22020927
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