AUTHOR=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 

TITLE=Decreased circulating branched-chain amino acids are associated with development of Alzheimer’s disease in elderly individuals with mild cognitive impairment

JOURNAL=Frontiers in Nutrition

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1040476

DOI=10.3389/fnut.2022.1040476

ISSN=2296-861X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Method</title><p>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,” <italic>N</italic> = 87) and converted to Alzheimer’s disease (AD) (“AD-convert,” <italic>N</italic> = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (<italic>APOE</italic> ε4) allele possession was also conducted.</p></sec><sec><title>Results</title><p>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 <italic>APOE</italic> ε4 possession (<italic>p</italic> &lt; 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the <italic>APOE</italic> ε4-negative group.</p></sec><sec><title>Conclusion</title><p>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 <italic>APOE</italic> 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.</p></sec><sec><title>Clinical trial registration</title><p>[<ext-link ext-link-type="uri" xlink:href="https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322" xmlns:xlink="http://www.w3.org/1999/xlink">https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322</ext-link>], identifier [UMIN000021965].</p></sec>