Spatial Navigation and APOE in Amnestic Mild Cognitive Impairment

Abstract

Background: The effect of APOE Ε4 allele (Ε4) on spatial navigation in amnestic mild cognitive impairment (aMCI) is unknown. Objective: Our purpose was to examine the characteristics of spatial navigation impairment in Ε4-positive (Ε4+) and Ε4-negative (Ε4–) aMCI subgroups. Methods: Blood samples were collected to determine the APOE genotype. A total of 34 aMCI patients were stratified into aMCI-Ε4– (n = 23) and aMCI-Ε4+ (n = 11) groups. Control (n = 28) and mild Alzheimer’s disease (AD; n = 16) groups were also used. We used a human analogue of the Morris water maze (enclosed arena 2.9 m in diameter) to examine body-centered (egocentric) and world-centered (allocentric) spatial navigation. Results: The aMCI-Ε4+ group performed poorer on spatial navigation than the aMCI-Ε4– group in both egocentric and allocentric tasks even though these 2 groups did not differ in global cognitive functioning or neuropsychological tests. The aMCI-Ε4+ and mild AD groups performed similarly on all Morris Water Maze tasks and were outperformed by the aMCI-Ε4– group, which also resembled the control group in performance on the egocentric tasks. The aMCI groups showed poor spatial navigation learning regardless of their Ε4 positivity. Conclusion: We found more profound deficits in spatial navigation in aMCI-Ε4+ relative to aMCI-Ε4– patients. The aMCI-Ε4+ group resembled the mild AD group in spatial navigation performance. Although the Ε4 genotype was indicative of spatial navigation performance, it was not indicative of the aMCI patients’ ability to learn the tasks. Spatial navigation testing represents a promising area with respect to identifying individuals at higher risk for AD among the heterogeneous MCI population.

Hippocampus-Related Cognitive Impairments in Young apoE4 Targeted Replacement Mice

“…The study revealed that the performance of the apoE4 mice in the object recognition and Morris water maze was impaired relative to that of the apoE3 mice and that it was also impaired in the contextual but not in the cued fear conditioning response.These findings are in accordance with previous results obtained utilizing a dry version of the Morris water maze and fear conditioning test results, which were obtained using young apoE4 mice [23,30]. They also extend previous studies that revealed that adult apoE4 mice are cognitively impaired [32,34,36,37,41,42,43,44] and suggest that, like in humans, the apoE4-driven cognitive impairments begin early in life [45,46]. …”

Human Analogue of the Morris Water Maze for Testing Subjects at Risk of Alzheimer’s Disease

“…The differences in spatial navigation observed in the aMCI subgroups in relation to ApoE4 status are in agreement with results yielded in animal research [6] and with controversial results yielded in bapineuzumab or rosiglitazone clinical trials. As our method has been found helpful in the diagnosis of MCI patients [7,8] we are developing computer tests which can be used in a broader clinical setting.…”

ApoE4 confers better spatial memory than apoE3 in young adult hAPP-Yac/apoE-TR mice

“…The second reason is that the effect of APOE-ε4 on spatial navigation performances has not been tested yet in young adults. A deleterious effect has been repeatedly shown in older adults [25,26] and only once in 7-10 years old children [27] when navigational place learning is not fully developed [28]. However, episodic memory, which depends crucially on the hippocampus and also includes spatial components of memorized events, is improved in young adult APOE-ε4 carriers, while impaired in older adults [5,29].…”