Impact of hyperhomocysteinemia and different dietary interventions on cognitive performance in a knock-in mouse model for Alzheimer’s disease

  • 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.

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Author:Hendrik NieraadORCiDGND, Natasja de BruinORCiD, Olga ArneORCiD, Martine C. J. HofmannORCiD, Mike Schmidt, Takashi SaitoORCiD, Takaomi C. Saido, Robert GurkeORCiDGND, Dominik Schmidt, Uwe Till, Michael J. ParnhamORCiDGND, Gerd GeisslingerORCiDGND
Parent Title (English):Nutrients
Place of publication:Basel
Document Type:Article
Date of Publication (online):2020/10/23
Date of first Publication:2020/10/23
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/11/16
Tag:Alzheimer’s disease; amyloid beta-peptides; animal; disease models; hyperhomocysteinemia; memory and learning tests; vitamin B deficiency
Page Number:27
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0