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Article

Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease

1
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Branch for Translational Medicine and Pharmacology TMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
2
Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Wako, Saitama 351-0198, Japan
3
Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan
4
pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
5
Former Institute of Pathobiochemistry, Friedrich-Schiller-University Jena, Nonnenplan 2, 07743 Jena, Germany
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(11), 3248; https://doi.org/10.3390/nu12113248
Received: 26 August 2020 / Revised: 13 October 2020 / Accepted: 20 October 2020 / Published: 23 October 2020
(This article belongs to the Special Issue Nutrition, Diet Quality, Aging and Frailty)
Background: Hyperhomocysteinemia is considered a possible contributor to the complex pathology of Alzheimer’s disease (AD). For years, researchers in this field have discussed the apparent detrimental effects of the endogenous amino acid homocysteine in the brain. In this study, the roles of hyperhomocysteinemia driven by vitamin B deficiency, as well as potentially beneficial dietary interventions, were investigated in the novel AppNL-G-F knock-in mouse model for AD, simulating an early stage of the disease. Methods: Urine and serum samples were analyzed using a validated LC-MS/MS method and the impact of different experimental diets on cognitive performance was studied in a comprehensive behavioral test battery. Finally, we analyzed brain samples immunohistochemically in order to assess amyloid-β (Aβ) plaque deposition. Results: Behavioral testing data indicated subtle cognitive deficits in AppNL-G-F compared to C57BL/6J wild type mice. Elevation of homocysteine and homocysteic acid, as well as counteracting dietary interventions, mostly did not result in significant effects on learning and memory performance, nor in a modified Aβ plaque deposition in 35-week-old AppNL-G-F mice. Conclusion: Despite prominent Aβ plaque deposition, the AppNL-G-F model merely displays a very mild AD-like phenotype at the investigated age. Older AppNL-G-F mice should be tested in order to further investigate potential effects of hyperhomocysteinemia and dietary interventions. View Full-Text
Keywords: hyperhomocysteinemia; vitamin B deficiency; Alzheimer’s disease; amyloid beta-peptides; disease models; animal; memory and learning tests hyperhomocysteinemia; vitamin B deficiency; Alzheimer’s disease; amyloid beta-peptides; disease models; animal; memory and learning tests
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MDPI and ACS Style

Nieraad, H.; de Bruin, N.; Arne, O.; Hofmann, M.C.J.; Schmidt, M.; Saito, T.; Saido, T.C.; Gurke, R.; Schmidt, D.; Till, U.; Parnham, M.J.; Geisslinger, G. Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease. Nutrients 2020, 12, 3248. https://doi.org/10.3390/nu12113248

AMA Style

Nieraad H, de Bruin N, Arne O, Hofmann MCJ, Schmidt M, Saito T, Saido TC, Gurke R, Schmidt D, Till U, Parnham MJ, Geisslinger G. Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease. Nutrients. 2020; 12(11):3248. https://doi.org/10.3390/nu12113248

Chicago/Turabian Style

Nieraad, Hendrik, Natasja de Bruin, Olga Arne, Martine C.J. Hofmann, Mike Schmidt, Takashi Saito, Takaomi C. Saido, Robert Gurke, Dominik Schmidt, Uwe Till, Michael J. Parnham, and Gerd Geisslinger. 2020. "Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease" Nutrients 12, no. 11: 3248. https://doi.org/10.3390/nu12113248

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