TY  - JOUR
A1  - Nieraad, Hendrik
A1  - Bruin, Natasja de
A1  - Arne, Olga
A1  - Hofmann, Martine C. J.
A1  - Schmidt, Mike
A1  - Saito, Takashi
A1  - Saido, Takaomi C.
A1  - Gurke, Robert
A1  - Schmidt, Dominik
A1  - Till, Uwe
A1  - Parnham, Michael J.
A1  - Geisslinger, Gerd
T1  - Impact of hyperhomocysteinemia and different dietary interventions on cognitive performance in a knock-in mouse model for Alzheimer’s disease
T2  - Nutrients
N2  - 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.
KW  - hyperhomocysteinemia
KW  - vitamin B deficiency
KW  - Alzheimer’s disease
KW  - amyloid beta-peptides
KW  - disease models
KW  - animal
KW  - memory and learning tests
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56836
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-568361
SN  - 2072-6643
VL  - 12
IS  - 3248
PB  - MDPI
CY  - Basel
ER  -