Affiliations: [a] Institute of Public Health, National Yang-Ming University, Taipei, Taiwan
| [b] Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA
| [c] Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA
| [d] Translational Gerontology Branch, National Institute on Aging, National Institute on Aging, Baltimore, MD, USA
| [e] Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA
Correspondence:
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Correspondence to: Madhav Thambisetty, MD, PhD, Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, Room 4B-311, 251 Bayview Blvd, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD 21224, USA. Tel.: +1 410 558 8572; Fax: +1 410 558 8674; E-mail: [email protected].
Abstract: Background:An epistatic interaction between the ɛ4 allele of apolipoprotein E (APOE ɛ4) and the K-variant of butyrylcholinesterase (BCHE-K) genes has been previously reported to increase risk of Alzheimer’s disease (AD). However, these observations were largely from case-control studies with small sample sizes. Objective:To examine the interaction between APOE ɛ4 and BCHE-K on: 1) the risk of incident AD and 2) rates of change in brain volumes and cognitive performance during the preclinical stages of AD in a prospective cohort study. Methods:The study sample for survival analysis included 691 Caucasian participants (age at baseline, 58.4±9.9 years; follow-up time,16.9±9.7 years) from the Baltimore Longitudinal Study of Aging. The neuroimaging sample included 302 participants with 1,388 brain magnetic resonance imaging (MRI) scans. Cognitive performance was assessed in 703 participants over 4,908 visits. Results:A total of 122 diagnoses (79 AD, 43 mild cognitive impairment [MCI]) were identified. Participants with both APOE ɛ4 and BCHE-K variants had a 3.7-fold greater risk of AD (Hazard ratio [HR] 95%, CI=1.99–6.89, p < 0.001) compared to non-carriers of both genes (APOE ɛ4 x BCHE-K interaction p = 0.025). There was no APOE ɛ4-BCHE-K interaction effect on rate of cognitive decline and brain atrophy. Conclusion:The APOE and BCHE genes interact to influence risk of incident AD/MCI but not rates of brain atrophy and decline in cognitive performance before onset of cognitive impairment. This may suggest that the epistatic interaction between APOE ɛ4 and BCHE-K on AD risk is disease stage-dependent.
