The test is routinely used in studies investigating the disease pathogenesis and progression, as well as in studies testing efficacy of therapeutic interventions 11, 12. Morris in 1983, is the gold standard memory test in rodents and a popular tool in the cognitive assessment of AD mice 10. The Morris Water Maze (MWM), which was originally introduced by Richard G. Impairments in spatial navigation may therefore serve as an early indicator of AD. Some studies even suggest that disorientated patients are more likely to progress from MCI to AD 8, 9. Furthermore, several studies show that deficits in spatial navigation and orientation are more specific in distinguishing AD from other forms of dementia than episodic memory deficits 6, 7. Patients with mild cognitive impairment (MCI) and patients in the early stages of symptomatic AD often get lost in unfamiliar as well as familiar places 2, 5. Spatial disorientation, often referred to as wandering, is one of the earliest symptoms of memory deficits in AD 1, 2, 3, 4. Therefore, analyzing search strategies in the Tg4-42 model can be a powerful tool for preclinical drug testing and identifying early therapeutic successes.Īlzheimer’s disease (AD), the most common form of dementia, is characterized by progressive cognitive decline and neurodegeneration. The spatial navigation impairments in young Tg4-42 mice are well in line with the hypometabolism and synaptic deficits in the hippocampus. Analyzing search strategies in the MWM allows to differentiate between hippocampus-dependent allocentric and hippocampus-independent egocentric search strategies. Furthermore, we could show that the spatial reference memory deficits in aged Tg4-42 animals are caused by the lack of allocentric and spatial strategies. However, a detailed analysis of the swimming strategies demonstrated allocentric-specific memory deficits in 3 month-old Tg4-42 mice before the onset of severe memory deficits. In contrast, conventional analysis of the MWM indicated an intact spatial memory in 3 month-old Tg4-42 mice. Conventional behavior analysis of escape latencies and quadrant preference revealed spatial memory and reference memory deficits in female 7 and 12 month-old Tg4-42 mice. Here we investigated the spatial memory of female 3, 7 and 12 month-old Alzheimer Tg4-42 mice in comparison to wild-type control animals. The Morris Water Maze (MWM) is used to study spatial learning in rodent models. Spatial disorientation is one of the earliest symptoms in Alzheimer’s disease and allocentric deficits can already be detected in the asymptomatic preclinical stages of the disease.
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