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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Nutrients - 12(2020), 11 vom: 23. Okt.

Sprache:

Englisch

Beteiligte Personen:

Nieraad, Hendrik [VerfasserIn]
de Bruin, Natasja [VerfasserIn]
Arne, Olga [VerfasserIn]
Hofmann, Martine C J [VerfasserIn]
Schmidt, Mike [VerfasserIn]
Saito, Takashi [VerfasserIn]
Saido, Takaomi C [VerfasserIn]
Gurke, Robert [VerfasserIn]
Schmidt, Dominik [VerfasserIn]
Till, Uwe [VerfasserIn]
Parnham, Michael J [VerfasserIn]
Geisslinger, Gerd [VerfasserIn]

Links:

Volltext

Themen:

0LVT1QZ0BA
1001-13-4
Alzheimer’s disease
Amyloid beta-Peptides
Amyloid beta-peptides
Animal
Disease models
Homocysteic acid
Homocysteine
Hyperhomocysteinemia
Journal Article
Memory and learning tests
Vitamin B deficiency

Anmerkungen:

Date Completed 19.04.2021

Date Revised 19.04.2021

published: Electronic

Citation Status MEDLINE

doi:

10.3390/nu12113248

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM316826634