Impact of APOE and BDNF Val66Met Gene Polymorphisms on Cognitive Functions in Patients with Amnestic Mild Cognitive Impairment

Article type: Research Article

Authors: Cechova, Katerina^{a; b; *} | Andel, Ross^{a; b; c} | Angelucci, Francesco^a | Chmatalova, Zuzana^{b; d} | Markova, Hana^{a; b} | Laczó, Jan^{a; b} | Vyhnalek, Martin^{a; b} | Matoska, Vaclav^e | Kaplan, Vojtech^e | Nedelska, Zuzana^{a; b} | Ward, David D.^{f; g} | Hort, Jakub^{a; b}

Affiliations: [a] Department of Neurology, Memory Clinic, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic | [b] International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic | [c] School of Aging Studies, University of South Florida, Tampa, FL, USA | [d] Department of Medical Chemistry and Clinical Biochemistry, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic | [e] Department of Clinical Biochemistry, Hematology and Immunology, Homolka Hospital, Prague, Czech Republic | [f] Department of Medicine, Division of Geriatric Medicine, Dalhousie University, Halifax, Nova Scotia, Canada | [g] Centre for Health Care of the Elderly, QEII Health Sciences Centre, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada

Correspondence: [*] Correspondence to: Katerina Cechova, Memory Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 15006, Prague, Czech Republic. Tel.: +420 22443 6854; Fax: +420 22443 6820; E-mail: [email protected].

Abstract:  Apolipoprotein (APOE) ɛ4 is a well-known risk factor for late-onset Alzheimer’s disease (AD), but other AD-related gene polymorphisms might also be important, such as the polymorphism within the brain-derived neurotrophic factor (BDNF) gene. Carriage of BDNF Val66Met has been associated with faster cognitive decline and greater hippocampal atrophy in cognitively normal elderly. Thus, we examined the effects of the concurrent presence of APOE and BDNF polymorphisms on cognitive functions and brain morphometry in amnestic mild cognitive impairment (aMCI) patients. 107 aMCI patients (mean age = 72.2) were recruited from the Czech Brain Aging Study and, based on APOE and BDNF genes polymorphisms, were divided into four groups: ɛ4–BDNFVal/Val (n = 37), ɛ4–BDNFMet (n = 19), ɛ4+BDNFVal/Val (n = 35), and ɛ4+BDNFMet (n = 16). All patients underwent clinical examination, magnetic resonance imaging, and complex neuropsychological battery. The combination of APOE ɛ4+ and BDNF Met was associated with significantly worse memory performance in immediate and delayed recall compared to other polymorphism groups. We did not observe increased atrophy in areas related to memory function in the ɛ4+BDNFMet group. Our findings suggest that carriage of ɛ4+BDNFMet is associated with more pronounced memory dysfunction, a typical feature of early AD, but not with structural brain changes in aMCI patients. These findings suggest that in APOE ɛ4/BDNF Met carriers, synaptic dysfunction affecting memory may precede pronounced structural changes.

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, Apolipoprotein E, brain-derived neurotrophic factor, cognition, gene polymorphism

DOI: 10.3233/JAD-190464

Journal: Journal of Alzheimer's Disease, vol. 73, no. 1, pp. 247-257, 2020