Basic Science and Pathogenesis.

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• All-trans retinoic acid (ATRA), a vitamin A metabolite, upregulates ADAM10, crucial for non-amyloidogenic APP cleavage.
• Investigating vitamin A derivatives for Alzheimer's Disease (AD) therapy is ongoing, but the impact of vitamin A deficiency on AD pathology remains unclear.
• RARE-LacZ mice, used for mapping retinoic acid signaling, were crossed with J20 AD model mice to assess dietary vitamin A deficiency effects.

Purpose of the Study:

• To investigate the effects of chronic dietary vitamin A deficiency on learning, memory, and ATRA signaling in the hippocampus of J20 AD model mice.
• To determine if vitamin A deficiency exacerbates Alzheimer's Disease pathology in a mouse model.

Main Methods:

• Mice were fed either a standard or vitamin A-deficient diet from weaning.
• Behavioral testing at 9-10 months included open-field, novel object location/recognition, water T-maze, and rotarod tests.
• Immunohistochemistry was performed on brain hemispheres to analyze ATRA signaling and Aβ plaque aggregation.

Main Results:

• Aβ plaques in the hippocampus of J20 mice disrupted dentate gyrus (DG) integrity and potentially interfered with ATRA signaling.
• J20 mice showed accelerated learning and improved memory retention in the water T-maze compared to wild-type littermates.
• Dietary vitamin A levels did not significantly affect the performance or pathology in either genotype.

Conclusions:

• Aβ aggregation in J20 mice correlates with altered ATRA signaling in the DG, suggesting a link between AD pathology and retinoid signaling.
• Further analysis of ongoing behavioral data will clarify the relationship between diet, behavior, and AD pathology in the DG.