Detecting spatial memory deficits beyond blindness in tg2576 Alzheimer mice

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• The tg2576 mouse model is widely used for Alzheimer's disease research.
• The Pde6b(rd1) (rd) mutation causes retinal degeneration, potentially confounding behavioral studies.
• B6:SJL genetic background is common for tg2576 mice, but susceptible to the rd mutation.

Purpose of the Study:

• To identify reliable behavioral tasks for assessing memory deficits in tg2576 mice on a B6:SJL background.
• To determine if the rd mutation impacts tg2576 mouse performance in cognitive tasks.
• To validate tasks for testing therapeutic interventions in Alzheimer's disease models.

Main Methods:

• Pilot study in wild-type mice.
• Assessment of 8- and 16-month-old tg2576 mice (with and without rd mutation) in various behavioral tasks.
• Tasks included water maze, Y-maze alternation, object recognition, olfactory discrimination, object configuration recognition, and Barnes maze.

Main Results:

• Water maze acquisition was impossible in rd homozygotes.
• Y-maze alternation, object recognition, and olfactory discrimination were unaffected by the transgene or rd mutation.
• Spatial memory retention was significantly impaired in tg2576 mice in object configuration recognition and Barnes maze tasks, independent of the rd mutation.

Conclusions:

• The rd mutation is a critical confounding factor in specific behavioral assays for tg2576 mice.
• Object configuration recognition and Barnes maze are suitable tasks for evaluating spatial memory deficits in tg2576 mice.
• These tasks are valuable for testing cognitive therapies in tg2576 and other mouse models with visual impairments.