循环中支链氨基酸水平降低与轻度认知障碍老年个体患阿尔茨海默病有关。
Decreased circulating branched-chain amino acids are associated with development of Alzheimer's disease in elderly individuals with mild cognitive impairment.
作者信息
Ikeuchi Takeshi, Kanda Mayuka, Kitamura Hitomi, Morikawa Fumiyoshi, Toru Shuta, Nishimura Chika, Kasuga Kensaku, Tokutake Takayoshi, Takahashi Tetsuya, Kuroha Yasuko, Miyazawa Nobuhiko, Tanaka Shin, Utsumi Kumiko, Ono Kenjiro, Yano Satoshi, Hamano Tadanori, Naruse Satoshi, Yajima Ryuji, Kawashima Noriko, Kaneko Chikako, Tachibana Hisatsugu, Yano Yuki, Kato Yumiko, Toue Sakino, Jinzu Hiroko, Kitamura Akihiko, Yokoyama Yuri, Kaneko Eiji, Yamakado Minoru, Nagao Kenji
机构信息
Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
Research Institute for Bioscience Products and Fine Chemicals, Ajinomoto Co., Inc., Kawasaki, Japan.
出版信息
Front Nutr. 2022 Dec 14;9:1040476. doi: 10.3389/fnut.2022.1040476. eCollection 2022.
BACKGROUND
Nutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants.
METHOD
In a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal ("MCI-stable," = 87) and converted to Alzheimer's disease (AD) ("AD-convert," = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 ( ε4) allele possession was also conducted.
RESULTS
Plasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and ε4 possession ( < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the ε4-negative group.
CONCLUSION
The PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status.
CLINICAL TRIAL REGISTRATION
[https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].
背景
营养流行病学研究表明，老年人饮食中蛋白质摄入不足与脑功能不佳有关。血浆游离氨基酸（PFAA）谱反映营养状况，可能具有预测认知功能未来变化的潜力。在此，我们报告了一项针对轻度认知障碍（MCI）参与者的3年纵向研究的2年中期分析结果。
方法
采用多中心前瞻性队列设计，招募MCI参与者并采集空腹血浆样本。根据采血后长达2年的认知功能临床评估，将MCI参与者分为两组：仍处于MCI状态或恢复为认知正常（“MCI稳定组”，n = 87）以及转化为阿尔茨海默病（AD）（“AD转化组”，n = 68）。比较两组的基线PFAA谱。还进行了基于载脂蛋白Eε4（ε4）等位基因携带情况的分层分析。
结果
AD转化组中所有9种必需氨基酸（EAA）的血浆浓度均较低。在EAA中，即使在对年龄、性别、体重指数（BMI）和ε4携带情况等潜在混杂因素进行调整的逻辑回归模型中，三种支链氨基酸（BCAA）、缬氨酸、亮氨酸和异亮氨酸以及组氨酸（His）仍表现出显著差异（P < 0.05）。在分层分析中，这四种EAA的血浆浓度差异在ε4阴性组中更为明显。
结论
PFAA谱，尤其是BCAA和His的降低，与MCI参与者发生AD有关，且在ε4阴性人群中差异更大，表明PFAA谱是AD发生的独立风险指标。测量PFAA谱可能对评估MCI人群中AD转化风险具有重要意义，可能反映营养状况。
临床试验注册
[https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322]，标识符[UMIN000021965]。
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