ApoE Navi

Influences of the APOE-ε4 genotype and other Alzheimer´s disease (AD) related genes on spatial navigation ability and its neural basis

General

The main aim is to investigate the relationship between spatial navigation deficits and the remapping of grid-cell-like representations in entorhinal cortex as well as place cell remapping in the hippocampus in APOE-ε4 allele carriers, and the influence of body-based cues on navigation performance.

Background and aims

Patients at risk for developing AD often show substantial impairments in spatial navigation, which has been associated with neuropathologies (i.e., amyloid and p-tau deposition) in the hippocampus and entorhinal cortex. How these pathological processes affect computations performed by spatially tuned cells such as place and grid cells remain poorly understood.

Recent findings in rodents are providing new insights onto the underlying mechanisms during the progression of the disease. For example, Jun et al. (2020) demonstrated that spatial tuning and remapping (the sensitivity to different contexts) are severely impaired in hippocampal place cells and entorhinal grid cells of APP knock-in mice, who show amyloid beta deposition in both regions. The question of whether this can be similarly observed in humans, who are at risk for AD, remains unknown, although it has been shown that young people who are at high risk for AD (i.e. APOE-ε4 allele gene carriers) exhibit reduced grid-cell like representations during spatial navigation (Kunz et al., 2015).

Thus, the present study aims to employ both behavioral and neuroimaging techniques to investigate the underlying cause of the navigation deficits in APOE-ε4 allele carriers and to measure the remapping of grid-cell-like representations in the entorhinal cortex and place cell remapping in the hippocampus.

Course of the study

3 visits (1 visit per day):

Day 1:Part 1 of a spatial navigation experiment during MRI scanning plus pre-tests (questionnaires, blood test, training of the navigation task before scanning)
(appr. 2 hours).
Day 2
(next day after visit 1)
Part 2 of the spatial navigation experiment during MRI scanning
(appr. 1.5 hours)
Day 3:behavioral path integration task
(appr. 1.5 hours)

 

Principle Investigators: Dr. Nadine Diersch (DZNE, Magdeburg), Dr. Hwee-Ling Lee (DZNE, Bonn)
Start of the study: 2018
Status: mono centric (DZNE Bonn), ongoing, recruiting active

Contact
Dr. Dr. Cornelia McCormick
+49 228 43302-807
Yilmaz Sagik
+49 228 43302-871

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