Abstract Background Nutrition is a pivotal factor in the prevention of dementia. Matcha green tea powder, which contains L‐theanine, caffeine, and epigallocatechin gallate, has the beneficial effects of each constituent on cognitive functions and mood. However, no long‐term clinical study has yet been performed to evaluate the effect of Matcha on psychological functions. Here, we performed a randomized, double‐blinded, placebo‐controlled, clinical study, conducted over 12 months, to investigate the effect of Matcha on cognitive functions and sleep quality. Furthermore, the relationship between blood and neuroimaging biomarkers and the effect of Matcha was investigated. Methods We recruited 939 community‐dwelling older adults aged 60–84 years and enrolled subjects with a diagnosis of subjective cognitive decline (SCD) and mild cognitive impairment (MCI). A total of 99 subjects (64 SCD, 35 MCI) were randomized, with 49 receiving Matcha (2 g/day, male 23, female 26) and 50 receiving placebo (male 20, female 30). The groups were adjusted for age, sex, and APOE 4 genotype. Cognitive functions were assessed by MMSE, MoCA, ADAS‐cog, RBANS, and the CNS Vital Signs computerized neurocognitive battery. Sleep quality was measured by the Pittsburg Sleep Quality Index (PSQI). Plasma biomarkers and neuroimaging (Amyloid PET, MRI, SPECT, fNIRS) were also assessed. The change of outcome variables from the baseline to 12‐month was tested statistically using a mixed‐effects model. Results Compared to the placebo, the consumption of Matcha induced a significant improvement in social acuity assessed by perception of facial emotion ( P = 0.034), while continuous performance showed a trend towards improvement. The PSQI differed by 0.86 between the groups, indicating an improvement in sleep quality in the Matcha group compared to the placebo group ( P = 0.087). The MMSE score showed a slight increase in the Matcha group. Amyloid PET SUVR showed no change from baseline to 12‐month in either group, while the plasma Aβ42 was reduced in the Matcha group, suggesting increased clearance of peripheral Aβ42. Conclusion Facial emotion recognition is impaired in cognitive impairment. This long‐term intervention study suggests that Matcha consumption can improve emotion perception and attention, and sleep quality in elderly adults with cognitive decline.
Aggregated amyloid fibrils can induce further polymerization of precursor proteins in vitro, thus providing a possible basis for propagation or transmission in the pathogenesis of amyloidoses. Previously, we postulated that the transmission of amyloid fibrils induces conformational changes of endogenous amyloid protein in mouse senile amyloidosis (Xing, Y., Nakamura, A., Chiba, T., Kogishi, K., Matsushita, T., Fu, L., Guo Z., Hosokawa, M., Mori, M., and Higuchi, K. (2001) Lab. Invest. 81, 493-499). To further characterize this transmissibility, we injected amyloid fibrils (AApoAII(C)) of amyloidogenic C type apolipoprotein A-II (APOAIIC) intravenously into 2-month-old SAMR1 mice, which have B type apolipoprotein A-II (APOAIIB), and develop few if any amyloid deposits spontaneously. 10 months after amyloid injection, deposits were detected in the tongue, stomach, intestine, lungs, heart, liver, and kidneys. The intensity of deposition increased thereafter, whereas no amyloid was detected in distilled water-injected SAMR1 mice, even after 20 months. The deposited amyloid was composed of endogenous APOAIIB with a different amyloid fibril conformation. The injection of these amyloid fibrils of APOAIIB (AApoAII(B)) induced earlier and more severe amyloidosis in SAMR1 mice than the injection of AApoAII(C) amyloid fibrils. Thus, AApoAII(C) from amyloidogenic mice could induce a conformational change of less amyloidogenic APOAIIB to a different amyloid fibril structure, which could also induce amyloidosis in the less amyloidogenic strain. These results provide important insights into the pathogenesis of amyloid diseases.
Lifestyle habits after middle age significantly impact the maintenance of cognitive function in older adults. Nutritional intake is closely related to lifestyle habits; therefore, nutrition is a pivotal factor in the prevention of dementia in the preclinical stages. Matcha green tea powder (matcha), which contains epigallocatechin gallate, theanine, and caffeine, has beneficial effects on cognitive function and mood. We conducted a randomized, double-blind, placebo-controlled clinical study over 12 months to examine the effect of matcha on cognitive function and sleep quality.
Data is accumulating to suggest that a certain amyloidosis including AA and mouse AApoAII amyloidosis are transmissible. It is postulated that invasion of preexisted amyloid seed into the hosts plays a critical role in the transmission. The degree of denaturation / degradation of amyloid fibrils were evaluated by thioflavine T fluorescence assay and electron microscopy of aliquot. Data is accumulating to suggest that a certain amyloidosis including AA and mouse AApoAII amyloidosis are transmissible. It is postulated that invasion of preexisted amyloid seed into the hosts plays a critical role in the transmission. In order to search for a measure to eliminate or attenuate amyloid-seeding activity, we evaluated inhibitory effects of several treatments and medical reagents on amyloid fibril in the mouse AApoAII transmission model system. Generally AApoAII amyloid deposition was decreased in mice administered with denatured fibrils as compared with that in mice administered native fibrils.
Preformed amyloid fibrils accelerate conformational changes of amyloid precursor proteins and result in rapid extension of amyloid fibrils in vitro. We injected various kinds of amyloid fibrils into mice with amyloidogenic apoAII gene ( Apoa2 C ). The most severe amyloid depositions were detected in the tissues of mice injected with mouse AApoAII(C) amyloid fibrils. Mild amyloid depositions were also detected in the tissues of mice that were injected with other types of fibrils, including synthetic peptides and recombinant proteins. However, no amyloid depositions were found in mice that were injected with non‐amyloid fibril proteins. These results demonstrated that a common structure of amyloid fibrils could serve as a seed for amyloid fibril formation in vivo.
Apolipoprotein A-II (apoA-II), an apolipoprotein in serum high-density lipoprotein, is a precursor of mouse senile amyloid fibrils. The liver has been considered to be the primary site of synthesis. However, we performed nonradioactive in situ hybridization analysis in tissue sections from young and old amyloidogenic (R1.P1- Apoa2 c ) and amyloid-resistant (SAMR1) mice and revealed that other tissues in addition to the liver synthesize apoA-II. We found a strong hybridization signal in the basal cells of the squamous epithelium and the chief cells of the fundic gland in the stomach, the crypt cells and a small portion of the absorptive epithelial cells in the small intestine, the basal cells of the tongue mucosa, and the basal cells of the epidermis and hair follicles in the skin in both mouse strains. Expression of apoA-II mRNA in those tissues was also examined by RT-PCR analysis. Immunolocalization of apoA-II protein also indicated the cellular localization of apoA-II. ApoA-II transcription was not observed in the heart. Amyloid deposition was observed around the cells expressing apoA-II mRNA in the old R1.P1- Apoa2 c mice. These results demonstrate that the apoA-II mRNA is transcribed and translated in various extrahepatic tissues and suggest a possible contribution of apoA-II synthesized in these tissues to amyloid deposition.
Journal Article Geranylgeranyl Diphosphate Synthase Catalyzing the Single Condensation between Isopentenyl Diphosphate and Farnesyl Diphosphate Get access Hiroshi Sagami, Hiroshi Sagami 2 Institute of Chemical Reaction Science, Tohoku UniversityKatahira, Aoba-ku, Sendai 980 2To whom correspondence should be addressed. Search for other works by this author on: Oxford Academic PubMed Google Scholar Tatsumi Korenaga, Tatsumi Korenaga Institute of Chemical Reaction Science, Tohoku UniversityKatahira, Aoba-ku, Sendai 980 Search for other works by this author on: Oxford Academic PubMed Google Scholar Kyozo Ogura Kyozo Ogura 2 Institute of Chemical Reaction Science, Tohoku UniversityKatahira, Aoba-ku, Sendai 980 2To whom correspondence should be addressed. Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 114, Issue 1, July 1993, Pages 118–121, https://doi.org/10.1093/oxfordjournals.jbchem.a124125 Published: 01 July 1993 Article history Received: 13 July 1992 Published: 01 July 1993
AApoAII amyloid fibrils have exhibited prion-like transmissibility in mouse senile amyloidosis. We have demonstrated that AApoAII is extremely active and can induce amyloidosis following doses less than 1 pg. We tested physical and chemical methods to disrupt AApoAII fibrils in vitro as determined by thioflavin T binding and electron microscopy (EM) as well as inactivating the transmissibility of AApoAII fibrils in vivo. Complete disruption of AApoAII fibrils was achieved by treatment with formic acid, 6 M guanidine hydrochloride, and autoclaving in an alkaline solution. Injection of these disrupted AApoAII fibrils did not induce amyloidosis in mice. Disaggregation with 6 M urea, autoclaving, and alkaline solution was incomplete, and injection of these AApoAII fibrils induced mild amyloidosis. Treatment with formalin, delipidation, freeze-thaw, and RNase did not have any major effect. A distinct correlation was obtained between the amounts of amyloid fibrils and the transmissibility of amyloid fibrils, thereby indicating the essential role of fibril conformation for transmission of amyloidosis. We also studied the inactivation of AApoAII fibrils by several organic compounds in vitro and in vivo. AApoAII amyloidosis provides a valuable system for studying factors that may prevent transmission of amyloid disease as well as potential novel therapies.
