The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism has been shown to moderate the extent to which memory decline manifests in preclinical Alzheimer's disease (AD). To date, no study has examined the relationship between BDNF and memory in individuals across biologically confirmed AD clinical stages (i.e., Aβ+). We aimed to understand the effect of BDNF on episodic memory decline and clinical disease progression over 126 months in individuals with preclinical, prodromal and clinical AD. Participants enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who were Aβ + (according to positron emission tomography), and cognitively normal (CN; n = 238), classified as having mild cognitive impairment (MCI; n = 80), or AD (n = 66) were included in this study. Cognition was evaluated at 18 month intervals using an established episodic memory composite score over 126 months. We observed that in Aβ + CNs, Met66 was associated with greater memory decline with increasing age and were 1.5 times more likely to progress to MCI/AD over 126 months. In Aβ + MCIs, there was no effect of Met66 on memory decline or on disease progression to AD over 126 months. In Aβ + AD, Val66 homozygotes showed greater memory decline, while Met66 carriers performed at a constant and very impaired level. Our current results illustrate the importance of time and disease severity to clinicopathological models of the role of BDNF Val66Met in memory decline and AD clinical progression. Specifically, the effect of BDNF on memory decline is greatest in preclinical AD and reduces as AD clinical disease severity increases.

中文翻译：

---

阿尔茨海默病范围内的 BDNF VAL66MET 多态性和记忆力下降

脑源性神经营养因子 ( BDNF ) Val66Met (rs6265) 多态性已被证明可以缓解临床前阿尔茨海默病 (AD) 中记忆力下降的程度。迄今为止，没有研究检查过生物学证实的 AD 临床阶段（即 Aβ+）个体的BDNF与记忆之间的关系。我们旨在了解BDNF的影响关于临床前、前驱和临床 AD 患者 126 个月内的情景记忆衰退和临床疾病进展。参加澳大利亚影像、生物标志物和生活方式 (AIBL) 研究的参与者为 Aβ +（根据正电子发射断层扫描）和认知正常（CN；n = 238），被归类为轻度认知障碍（MCI；n = 80） , 或 AD (n = 66) 包括在本研究中。使用超过 126 个月的已建立的情景记忆综合评分，每隔 18 个月评估一次认知。我们观察到，在 Aβ + CNs 中，Met66 与随着年龄的增长而出现更大的记忆力下降有关，并且在 126 个月内进展为 MCI/AD 的可能性是其 1.5 倍。在 Aβ + MCI 中，Met66 在 126 个月内对记忆力下降或疾病进展为 AD 没有影响。在 Aβ + AD 中，Val66 纯合子表现出更大的记忆力下降，而 Met66 携带者表现出恒定且非常受损的水平。我们目前的结果说明了时间和疾病严重程度对临床病理学模型的重要性BDNF Val66Met 在记忆衰退和 AD 临床进展中的作用。具体而言，BDNF对记忆衰退的影响在临床前 AD 中最大，并且随着 AD 临床疾病严重程度的增加而降低。