著者

Toshifumi Nanjo Takaomi Fukuhara Naoko Kameshima Daijiro Yanagisawa Shino Shimizu Takeshi Shimizu Akihiko Shiino Hiroyasu Akatsu Takayuki Yamamoto Ikuo Tooyama

出版者

Japan Brain Science society

雑誌

脳科学誌 (ISSN:13415301)

巻号頁・発行日

vol.44, pp.5-23, 2014-12-30 (Released:2017-06-01)

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Previous studies have reported that β-amyloid peptides (Aβ) are observed in the nasal mucosa of postmortem human samples. In a mouse model of Alzheimer's disease (AD), nasal Aβ levels positively correlate with insoluble Aβ levels in the brain. However, it is difficult to measure Aβ content in human nasal smears. Here we report a novel and sensitive method of measuring Aβ42 content in the human nasal cavity and its application in normal human volunteers. We collected nasal smears by cotton swab from the mucosa of the inferior nasal concha and common nasal meatus of 26 normal volunteers with an age range of 23-78 years. The swabs were placed in microtubes and extracted with pure water. Extract solution was removed from each sample for protein assay and the remaining sample was added with formic acid, incubated at 70℃ for one hour, and then centrifuged in a centrifugal filter device to remove larger protein complexes and cellular debris. The filtrates were concentrated and then buffered before Aβ42 concentrations were measured using a commercially available ELISA kit. Samples from five volunteers were also assayed for Aβ42 content without pretreatment. Our novel method for collecting and assaying nasal mucosal smears enabled us to measure Aβ42 content in both the inferior nasal concha and the common nasal meatus of all cases examined, despite the levels being under detection limits (0.1 pmol/L) without pretreatment. There was significantly more Aβ42 content per gram of total protein in the inferior nasal concha (12.37 ± 5.98 pmol/g) than in the common nasal meatus (3.58 ± 1.94 pmol/g; P < 0.001). Thus, this method would be useful for AD screening.

著者

Toshifumi Nanjo Takaomi Fukuhara Naoko Kameshima Daijiro Yanagisawa Shino Shimizu Takeshi Shimizu Akihiko Shiino Hiroyasu Akatsu Takayuki Yamamoto Ikuo Tooyama

出版者

Japan Brain Science society

雑誌

脳科学誌 (ISSN:13415301)

巻号頁・発行日

vol.42, pp.5-20, 2013-09-30 (Released:2017-06-01)

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Previous studies reported that β-amyloid peptides (Aβ) were observed in nasal mucosa of postmortem human samples. In the model mouse of Alzheimer's disease (AD), nasal Aβ levels positively correlate with insoluble Aβ levels in the brain. However, it is difficult to measure Aβ content in human nasal smears. Here we have reported a novel and sensitive method of measuring Aβ42 content in the human nasal cavity. We collected nasal smears by cotton swab from the mucosa of the inferior nasal concha and common nasal meatus of 13 normal volunteers with an age range of 30-78 years. The swabs were put into microtubes and the protein content extracted with 700 μL of 80% formic acid. Ten microliters of the extract solution was removed from each sample to assay protein levels. The remaining 690 μL was incubated at 70℃ for one hour, transferred to a centrifugal filter device, and centrifuged for one hour at 14000 g to remove larger protein complexes and cellular debris. The filtrates were concentrated to 20 μL, and then neutralized by adding 480 μL of 1 M Tris. Finally, the Aβ42 protein concentrations were measured using a commercially available ELISA kit, with the samples from five volunteers assayed for Aβ42 content without pretreatment. Our novel method for collecting and assaying nasal mucosal smears enabled us to measure Aβ42 content in both the inferior nasal concha and the common nasal meatus of all cases examined here, despite the levels being under detection limits (0.5 pmol/L) without pretreatment. The mean levels of Aβ42 per total protein in the inferior nasal concha and common nasal meatus of normal controls were 6.24 ± 3.70 fmol/g and 2.10 ± 0.77 fmol/g, respectively. Thus, there was significantly more Aβ42 content per total protein in the inferior nasal concha than in the common nasal meatus (P<0.01). Thus, this method would be useful for AD screening.

著者

Yasuhide Iwata Shigeyuki Yamamoto Ikuo Tooyama Shu Takagai Kiyokazu Takebayashi Norio Mori

出版者

Japan Brain Science society

雑誌

脳科学誌 (ISSN:13415301)

巻号頁・発行日

vol.37, pp.16-27, 2011 (Released:2017-06-01)

参考文献数

31

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The numbers of brain tumors survivors who receive whole-brain irradiation (WBI) develop progressive cognitive dysfunction. WBI-induced decrease in neurogenesis in hippocampus is involved in the delayed cognitive impairment. Considerable data suggests that the continuous suppression of neurogenesis may be due to the activated microglia. To clarify the mechanisms of the radiation-induced deficits in cognitive function, we studied an early response of the hippocampal proliferating cells to the WBI. Adult cynomolgus monkeys received fractionated WBI with the total dose of 15Gy and 30Gy. The animals were administrated with BrdU to label proliferating cells five days after the WBI and sacrificed on the next day. The density of proliferating cells in the hippocampus was significantly increased (ANOVA, F=23, df=2, 9, p=0.0003). Comparing to the sham-irradiation, proliferation were elevated by 6.3 and 12.6 times with 15Gy and 30Gy, respectively. However, there is no BrdU (+) cells co-labeled with Iba1, which is a marker of microglia. The radiation-induced cell proliferation in the hippocampus may play a contributory role in the pathogenesis of late delayed cognitive dysfunction after the WBI.

著者

Akira Fujiyoshi Katsuyuki Miura Takayoshi Ohkubo Naoko Miyagawa Yoshino Saito Itsuko Miyazawa Akihiko Shiino Aya Kadota Sayaka Kadowaki Takashi Hisamatsu Sayuki Torii Naoyuki Takashima Ikuo Tooyama Hirotsugu Ueshima

出版者

Japan Epidemiological Association

雑誌

Journal of Epidemiology (ISSN:09175040)

巻号頁・発行日

pp.JE20180258, (Released:2019-05-25)

参考文献数

46

被引用文献数

10

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Background: The association of proteinuria and reduced estimated glomerular filtration rate (eGFR) with cognition needs more clarification. We cross-sectionally examined whether proteinuria and reduced eGFR, even in moderate stages, were independently associated with lower cognition in a community-based sample of elderly men.Methods: Our cohort initially comprised 1,094 men aged 40-79 years from a random sample from Shiga, Japan in 2006-2008. Of 853 men who returned for the follow-up examination (2009-2014), we analyzed 561 who were ≥65 years, free of stroke, and completed the Cognitive Abilities Screening Instrument (CASI) at follow-up. Higher CASI score (range 0 to 100) indicates better cognition. Proteinuria was assessed by dipstick. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration Equation. Participants were divided into three groups either by eGFR (≥60, 59-40, and <40 mL/min/1.73 m2) or by proteinuria (no, trace, and positive), considered normal, moderate, and advanced, respectively. Using linear regression, we computed mean CASI score with simultaneous adjustment for proteinuria and eGFR in addition to other potential confounders.Results: Significant trends of lower cognition were observed across the groups of worse proteinuria and lower eGFR independently: multivariable-adjusted mean CASI scores were 90.1, 89.3, and 88.4 for proteinuria (Ptrend=0.029), and 90.0, 88.5, and 88.5 for eGFR (Ptrend=0.015) in mutual adjustment model.Conclusions: Proteinuria and reduced eGFR, even in their moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. The results suggest the importance of proteinuria and low eGFR for early detection and prevention of cognitive decline.

著者

Ziyi Liu Maryam Zaid Takashi Hisamatsu Sachiko Tanaka Akira Fujiyoshi Naoko Miyagawa Takahiro Ito Aya Kadota Ikuo Tooyama Katsuyuki Miura Hirotsugu Ueshima

出版者

Japan Epidemiological Association

雑誌

Journal of Epidemiology (ISSN:09175040)

巻号頁・発行日

pp.JE20180193, (Released:2019-05-25)

参考文献数

34

被引用文献数

7

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BackgroundCognitive dysfunction has been recognized as a diabetes-related complication. Whether hyperglycemia or elevated fasting glucose are associated with cognitive decline remains controversial. We aimed to investigate the relationship between fasting glucose levels and cognitive function in diabetic and non-diabetic individuals.MethodsParticipants were Japanese diabetic (n=191) and non-diabetic (n=616) men, aged 46-81 years, from 2010-2014. Blood samples were taken after a 12h fast. Cognitive Ability Screening Instrument (CASI), with a maximum score of 100, was used for cognitive assessment. Cognitive domains of CASI were also investigated. Fractional logit regression with covariate adjustment for potential confounders was used to model cross-sectional relationships between fasting blood glucose and CASI score.ResultsFor diabetic individuals, CASI score was 0.38 (95% confidence interval: 0.66-0.12) lower per 1mmol/L higher fasting glucose level. Short-term memory domain also exhibited an inverse association. For non-diabetic individuals, a reverse u-shaped relationship was observed between fasting glucose and cognitive function, identifying a threshold for highest cognitive performance of 91.8 CASI score at 3.97-6.20mmol/L (71.5-111.6mg/dL) fasting glucose. Language ability domain displayed a similar relationship with fasting glucose.ConclusionsElevated fasting glucose levels in diabetic men were associated with lower cognitive function, in which short-term memory was the main associated domain. Interestingly, in non-diabetic men, we identified a threshold for the inverse relationship of elevated fasting glucose with cognitive function. Contrastingly to diabetic men, language ability was the main associated cognitive domain.

著者

Yuyan Liu Akira Fujiyoshi Hisatomi Arima Aya Kadota Sayaka Kadowaki Takashi Hisamatsu Itsuko Miyazawa Keiko Kondo Ikuo Tooyama Katsuyuki Miura Hirotsugu Ueshima for the SESSA Research Group

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.47977, (Released:2019-05-15)

参考文献数

43

被引用文献数

4

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Aim: Computed tomography (CT) can directly provide information on body compositions and distributions, compared to anthropometric indices. It has been shown that various obesity indices are associated with carotid intima-media thickness (IMT). However, whether CT-based obesity indices are stronger than anthropometric indices in association with atherosclerosis remains to be determined in a general population.Methods: We cross-sectionally assessed carotid IMT using ultrasound in 944 community-dwelling Japanese men free of stroke and myocardial infarction. CT image at the L4–L5 level was obtained to compute areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Anthropometric measures assessed included body mass index (BMI), waist circumference, and waist-to-hip ratio. Using multivariable linear regression, slopes of IMT per 20th to 80th percentile of each index were compared. We also compared the slope of index with simultaneous adjustment for BMI in the same model.Results: Areas of VAT and SAT were positively associated with IMT, but not stronger than those of anthropometric indices in point estimates. Among all obesity indices, BMI was strongest in association with IMT after adjusting for age and lifestyle factors or further adjusting for metabolic factors. In simultaneous adjustment models, BMI, but not CT-based indices, remained significant and showed the strongest association.Conclusions: In community-dwelling Japanese men, anthropometric obesity indices, BMI in particular, were more strongly associated with carotid atherosclerosis than CT-based obesity indices. The association of general obesity with carotid atherosclerosis was strong and adding CT-based obesity measure did not considerably influence in the association.

著者

Tomone AMATSUBO Daijiro YANAGISAWA Shigehiro MORIKAWA Hiroyasu TAGUCHI Ikuo TOOYAMA

出版者

日本磁気共鳴医学会

雑誌

Magnetic Resonance in Medical Sciences (ISSN:13473182)

巻号頁・発行日

vol.9, no.3, pp.95-99, 2010 (Released:2010-09-27)

参考文献数

23

被引用文献数

9 21

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The formation of senile plaques followed by deposition of amyloid β peptides (Aβ) are the earliest pathological changes of Alzheimer's disease (AD); thus, detection of the plaques remains the most important early diagnostic indicator of AD. Amyloid imaging is a noninvasive technique for visualizing senile plaques in the brains of patients with Alzheimer's using positron emission tomography (PET) or magnetic resonance (MR) imaging. Several types of probes have been developed for PET, but few ligands have been developed specifically for MR imaging detection of amyloid plaques. This review presents recent advances in amyloid imaging using MR imaging and includes our studies.