The Influence of BDNF Val66Met Polymorphism on Cognition, Cerebrospinal Fluid, and Neuroimaging Markers in Non-Demented Elderly

Article type: Research Article

Authors: Xia, Hui^{a; 1} | Wang, Min^{b; 1} | Li, Jie-Qiong^a | Tan, Chen-Chen^a | Cao, Xi-Peng^c | Tan, Lan^{a; *} | Yu, Jin-Tai^{d; *} | Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, China | [b] College of Nursing, Qingdao University, China | [c] Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, China | [d] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Jin-Tai Yu, MD, PhD, Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 Wulumuqi Road, Shanghai, China. Tel.: +86 532 8890 5659; Fax: +86 532 8890 5659; E-mail: [email protected] and Dr. Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, China. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] Data used in preparation for this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Background:The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism emerged as a risk factor for Alzheimer’s disease (AD). However, little was known about its effects on the process of potential AD. Objective:To explore the effects of the Val66Met polymorphism on cognition, cerebrospinal fluid (CSF), and neuroimaging markers in non-demented elderly individuals. Methods:A total of 1,081 adults without dementia (375 healthy subjects and 706 individuals with mild cognitive impairment) were recruited from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to test the influence of BDNF Val66Met polymorphism on cognitive impairment, brain structure atrophy, and change in the levels of CSF biomarkers. Moreover, we also conducted our study in abnormal amyloid-β (A+) subgroup and normal amyloid-β (A–) subgroup, as well as in APOE ɛ4 carriers and non-carriers. Results:The BDNF Val66Met polymorphism had significant association with atrophy of the entorhinal cortex and Mini-Mental State Examination (MMSE) scores in the non-demented elderly and A + subgroup, while no association was found in A–subgroup. What is more, there was a significant effect of interaction between BDNF Val66Met and amyloid-β load in MMSE. In addition, significant associations of BDNF Val66Met with the entorhinal cortex and ventricular volumes were found among APOE ɛ4 non-carriers, but not APOE ɛ4 carriers. Conclusions:The BDNF Val66Met polymorphism is associated with cognitive impairment and brain atrophy among the non-demented elderly, APOE ɛ4 non-carriers and A + subgroup, implying the potential of the Val66Met polymorphism as an important genetic factor for AD-related neurodegeneration.

Keywords: Alzheimer’s disease, amyloid-β, brain-derived neurotrophic factor, polymorphism

DOI: 10.3233/JAD-180971

Journal: Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 405-414, 2019