Mayo Clinic Graduate School of Biomedical Sciences, Clinical and Translational Science Track, Scottsdale, AZ, USA.
Translational neuroscience and Aging Laboratory, Mayo Clinic, Scottsdale, AZ, USA.
J Alzheimers Dis. 2020;78(2):721-734. doi: 10.3233/JAD-200132.
Whether brain-derived neurotrophic factor (BDNF) Met carriage impacts the risk or progression of Alzheimer's disease (AD) is unknown.
To evaluate the interaction of BDNF Met and APOE4 carriage on cerebral metabolic rate for glucose (CMRgl), amyloid burden, hippocampus volume, and cognitive decline among cognitively unimpaired (CU) adults enrolled in the Arizona APOE cohort study.
114 CU adults (mean age 56.85 years, 38% male) with longitudinal FDG PET, magnetic resonance imaging, and cognitive measures were BDNF and APOE genotyped. A subgroup of 58 individuals also had Pittsburgh B (PiB) PET imaging. We examined baseline CMRgl, PiB PET amyloid burden, CMRgl, and hippocampus volume change over time, and rate of change in cognition over an average of 15 years.
Among APOE4 carriers, BDNF Met carriers had significantly increased amyloid deposition and accelerated CMRgl decline in regions typically affected by AD, but without accompanying acceleration of cognitive decline or hippocampal volume changes and with higher baseline frontal CMRgl and slower frontal decline relative to the Val/Val group. The BDNF effects were not found among APOE4 non-carriers.
Our preliminary studies suggest that there is a weak interaction between BDNF Met and APOE4 on amyloid-β plaque burden and longitudinal PET measurements of AD-related CMRgl decline in cognitively unimpaired late-middle-aged and older adults, but with no apparent effect upon rate of cognitive decline. We suggest that cognitive effects of BDNF variants may be mitigated by compensatory increases in frontal brain activity-findings that would need to be confirmed in larger studies.
脑源性神经营养因子（BDNF）Met 携带是否会影响阿尔茨海默病（AD）的风险或进展尚不清楚。
评估 BDNF Met 和 APOE4 携带对认知正常（CU）的亚利桑那 APOE 队列研究参与者的脑葡萄糖代谢率（CMRgl）、淀粉样蛋白负担、海马体积和认知下降的交互作用。
对 114 名 CU 成年人（平均年龄 56.85 岁，38%为男性）进行了纵向 FDG PET、磁共振成像和认知测量，并进行了 BDNF 和 APOE 基因分型。58 名个体还进行了匹兹堡 B（PiB）PET 成像。我们检查了基线 CMRgl、PiB PET 淀粉样蛋白负担、CMRgl 和海马体积随时间的变化，以及平均 15 年的认知变化率。
在 APOE4 携带者中，BDNF Met 携带者的淀粉样蛋白沉积明显增加，AD 常受影响区域的 CMRgl 下降加速，但认知下降或海马体积变化没有加速，与 Val/Val 组相比，基线额叶 CMRgl 更高，额叶下降更慢。在 APOE4 非携带者中未发现 BDNF 的作用。
我们的初步研究表明，在认知正常的中老年和老年人中，BDNF Met 和 APOE4 之间存在较弱的相互作用，对淀粉样蛋白-β斑块负担和 AD 相关的 CMRgl 下降的纵向 PET 测量有影响，但对认知下降的速度没有明显影响。我们认为，BDNF 变体的认知影响可能被额叶大脑活动的代偿性增加所缓解——这一发现需要在更大的研究中得到证实。
