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

BackgroundNutritional 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.MethodIn 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,” N = 87) and converted to Alzheimer’s disease (AD) (“AD-convert,” N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted.ResultsPlasma 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 APOE ε4 possession (p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group.ConclusionThe PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE 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]

Biological studies using mammalian cell lines and the current status of the microbeam irradiation system, SPICE

A microbeam irradiation system, SPICE (Single Particle Irradiation system to Cell), is under completion at the National Institute of Radiological Sciences (NIRS). We have improved the beam size, which is now approximately 5 micrometers diameter, and the cell targeting system, which can irradiated maximum of 400~500 cells per minute. Two types of cell dish were specially designed. One is Si3N4 plate (3mmx3mm area with 1 micrometer thickness) consisting of 7.5 mmx7.5 mm frame of 200 micrometer thickness, and the another is Mylar film stretched by pressing with a metal ring. These cell dishes can be set on the voice coil stage equipped on the cell targeting system, which also consist of a fluorescent microscope and a CCD camera for capturing the cell image. This microscope system captures all the image of dyed cell nuclei and computes the coordinates of the cell position according to the fluorescence and synchronizes this with a single particle irradiation system consisting of a scintillation counter and a beam deflector for irradiation. All the procedures can automatically be performed after setting some parameters, such as a preset number of protons. The first experiment was reported a visualization of phosphorylated histone protein, gamma-H2AX, which is known as a marker for DNA double strand breaks to confirm whether the targeted cell was accurately irradiated.[1] We also achieved a result showing the production of intracellular reactive oxygen species using DCF-DA as a fluorescent marker in irradiated CHO-K1 cells. Now we are focusing on low dose effects and how to obtain survival curves to measure hyper-radio sensitivity by irradiating CHO-K1 cell lines and its DNA repair deficient cell lines.11th International Conference on Nuclear Microprobe Technology and Application