The Combined Effect of APOE and BDNF Val66Met Polymorphisms on Spatial Navigation in Older Adults

Jan Laczó; Katerina Cechova; Martina Parizkova; Ondrej Lerch; Ross Andel; Vaclav Matoska; Vojtech Kaplan; Veronika Matuskova; Zuzana Nedelska; Martin Vyhnalek; Jakub Hort

doi:10.3233/JAD-200615

The Combined Effect of APOE and BDNF Val66Met Polymorphisms on Spatial Navigation in Older Adults

J Alzheimers Dis. 2020;78(4):1473-1492. doi: 10.3233/JAD-200615.

Authors

Jan Laczó^{1

2}, Katerina Cechova^{1

2}, Martina Parizkova^{1

2}, Ondrej Lerch^{1

2}, Ross Andel^{1

2

3}, Vaclav Matoska⁴, Vojtech Kaplan⁴, Veronika Matuskova^{1

2}, Zuzana Nedelska^{1

2}, Martin Vyhnalek^{1

2}, Jakub Hort^{1

2}

Affiliations

¹ Memory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
² International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.
³ School of Aging Studies, University of South Florida, Tampa, FL, USA.
⁴ Department of Clinical Biochemistry, Hematology and Immunology, Homolka Hospital, Prague, Czech Republic.

Abstract

Background: The apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory and spatial navigation deficits. The brain-derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment in APOEɛ4 carriers but its role in APOEɛ4-related spatial navigation deficits has not been established.

Objective: We examined influence of APOE and BDNF Val66Met polymorphism combination on spatial navigation and volumes of selected navigation-related brain regions in cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (aMCI).

Methods: 187 participants (aMCI [n = 116] and CU [n = 71]) from the Czech Brain Aging Study were stratified based on APOE and BDNF Val66Met polymorphisms into four groups: ɛ4-/BDNFVal/Val, ɛ4-/BDNFMet, ɛ4+/BDNFVal/Val, and ɛ4+/BDNFMet. The participants underwent comprehensive neuropsychological examination, brain MRI, and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real-space human analogue of the Morris water maze.

Results: Among the aMCI participants, the ɛ4+/BDNFMet group had the least accurate egocentric navigation performance (p < 0.05) and lower verbal memory performance than the ɛ4-/BDNFVal/Val group (p = 0.007). The ɛ4+/BDNFMet group had smaller hippocampal and entorhinal cortical volumes than the ɛ4-/BDNFVal/Val (p≤0.019) and ɛ4-/BDNFMet (p≤0.020) groups. Among the CU participants, the ɛ4+/BDNFMet group had less accurate allocentric and allocentric delayed navigation performance than the ɛ4-/BDNFVal/Val group (p < 0.05).

Conclusion: The combination of APOEɛ4 and BDNF Met polymorphisms is associated with more pronounced egocentric navigation impairment and atrophy of the medial temporal lobe regions in individuals with aMCI and less accurate allocentric navigation in CU older adults.

Keywords: Alzheimer’s disease; Morris water maze; apolipoproteins E; brain-derived neurotrophic factor; entorhinal cortex; episodic memory; gene polymorphism; magnetic resonance imaging; mild cognitive impairment; spatial navigation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Apolipoprotein E4 / genetics*
Brain-Derived Neurotrophic Factor / genetics*
Cognitive Dysfunction / genetics*
Cognitive Dysfunction / physiopathology
Female
Humans
Male
Middle Aged
Polymorphism, Genetic
Spatial Navigation / physiology*

Substances

Apolipoprotein E4
Brain-Derived Neurotrophic Factor
BDNF protein, human