A study of functional abilities in transgenic mouse models of Alzheimer's disease /

The appropriateness of three animal models in mimicking pathophysiology and symptoms of Alzheimer's disease was assessed. Behavioural tasks provided measures of cognitive function, affective behaviour and locomotor ability. Adult and aged transgenic mice, expressing the C104 fragment of the human $ beta$-Amyloid Precursor Protein, displayed increased anxiety by seven months of age in the Thatcher-Britton Novelty Conflict paradigm, memory impairments in the Forced Alternation T-Maze, the Porsolt Forced Swim test and the Recognition test, and decreased hippocampal acetylcholinesterase staining. BIBN99, a muscarinic M2-antagonist that increases release of acetylcholine, failed to ameliorate these changes. Apolipoprotein E deficient mice showed impairments of spatial memory in the Morris swim maze, but were unaffected by the administration of tacrine, an acetylcholinesterase inhibitor. Segmental trisomy 16 mice, a model of Down Syndrome and Alzheimer's disease, showed increases in hippocampal choline acetyl-transferase activity and mild memory impairments in the swim maze. BIBN99 had no effect on this deficit. These findings suggest that each of these models is beneficial in its own right for studying the functional deficits associated with Alzheimer's disease