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Toshifumi Matsui

Publications and source records attributed to Toshifumi Matsui.

At least 19 recordsLinked to original sources
PubMed2006

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing.

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.

ADP-Ribosylation Factors↗
PubMed2006

No alteration in tau exon 10 alternative splicing in tangle-bearing neurons of the Alzheimer's disease brain.

Defective splicing of tau mRNA, promoting a shift between tau isoforms with (4R tau) and without (3R tau) exon 10, is believed to be a pathological consequence of certain tau mutations causing frontotemporal dementia. By assessing protein and mRNA levels of 4R tau and 3R tau in 27 AD and 20 control temporal cortex, we investigated whether altered tau splicing is a feature also in Alzheimer's disease (AD). However, apart from an expected increase of sarcosyl-insoluble tau in AD, there were no significant differences between the groups. Next, by laser-capture microscopy and quantitative PCR, we separately analyzed CA1 hippocampal neurons with and without neurofibrillary pathology from six of the AD and seven of the control brains. No statistically significant differences in 4R tau/3R tau mRNA were found between the different subgroups. Moreover, we confirmed the absence of significant ratio differences in a second data set with laser-captured entorhinal cortex neurons from four AD and four control brains. Finally, the 4R tau/3R tau ratio in CA1 neurons was roughly half of the ratio in temporal cortex, indicating region-specific differences in tau mRNA splicing. In conclusion, this study indicated region-specific and possibly cell-type-specific tau splicing but did not lend any support to overt changes in alternative splicing of tau exon 10 being an underlying factor in AD pathogenesis.

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PubMed2006

Dietary intakes and plasma 8-iso-prostaglandin F2alpha concentrations in community-dwelling elderly Japanese: the Tsurugaya project.

We examined the association between dietary intakes and oxidative stress status in elderly Japanese. We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment conducted in 2002. The subjects included 961 Japanese subjects aged 70 years or older who were non-daily antioxidant supplements users. We measured plasma total 8-iso-prostaglandin (PG)F(2alpha) concentrations, a measurable lipid peroxidation biomarker, using a specific enzyme immunoassay kit. Dietary intakes were assessed through a food frequency questionnaire. Subjects were divided into three groups according to their dietary intake frequencies. Logistic regression was applied to calculate the odds ratios (ORs) for being in the highest tertile of plasma 8-iso-PGF(2alpha) concentration. Frequent intake of orange or other citrus fruits, or persimmon, strawberry, or kiwi fruit was associated with lower plasma 8-iso-PGF(2alpha) concentrations, respectively. After adjustment for potential confounders, the ORs and 95% confidence intervals (CIs) for orange or other citrus fruits were 1.00 (reference), 0.66 (0.47, 0.92), and 0.58 (0.39, 0.87) (p for trend, 0.009). Intake of persimmon, strawberry, or kiwi fruit showed similar results. These associations were partly explained by vitamin C intake. Other dietary intakes had no association. Intake of fruits may have a beneficial effect against oxidative stress in elderly Japanese.

Age Factors↗
PubMed2006

Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1.

BACKGROUND: Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available. OBJECTIVE: The objective was to examine the association between green tea consumption and cognitive function in humans. DESIGN: We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of <28, <26, and <24 and calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment. RESULTS: Higher consumption of green tea was associated with a lower prevalence of cognitive impairment. At the <26 cutoff, after adjustment for potential confounders, the ORs for the cognitive impairment associated with different frequencies of green tea consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI: 0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72) for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24. CONCLUSION: A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.

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PubMed2006

Coordinated expression of caspase 8, 3 and 7 mRNA in temporal cortex of Alzheimer disease: relationship to formic acid extractable abeta42 levels.

Recent studies support the hypothesis that Alzheimer disease (AD)-associated amyloid-beta protein (Abeta) may induce apoptosis mediated by a caspase cascade. To assess whether mRNA levels of caspase-3, 7, 8 and 9 change in AD brain, and whether these changes correlate with neurofibrillary tangles, Abeta40 or Abeta42 protein levels or senile plaques, 25 AD and 21 non-demented control brains were examined. Elevated mRNA levels of caspases-7 and 8 measured by a quantitative PCR method were observed in the AD temporal neocortex as compared to the control brains. No significant differences were noticed in levels of caspases-3 or 9 between AD and control brains. Multiple regression analysis demonstrated that, within subjects, the mRNA levels of caspase-8 strongly correlated with both caspse-3 and caspase-7 independently of postmortem interval. Further, there was a strong positive correlation of caspase-8 levels with formic acid extractable Abeta42 levels. Our results suggest that the transcriptional activation of key components of the apoptotic cascade correlates with accumulation of Abeta 42. Thus, a principal caspase pathway from caspase-8 to caspase-3 and/or 7 may contribute to neuron loss in AD brain.

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PubMed2005

Cerebrospinal fluid neprilysin is reduced in prodromal Alzheimer's disease.

Amyloid beta peptide (A beta) has been implicated in Alzheimer's disease (AD) as an initiator of the pathological cascades. Several lines of compelling evidence have supported major roles of A beta-degrading enzyme neprilysin in the pathogenesis of sporadic AD. Here, we have shown a substantial reduction of cerebrospinal fluid (CSF) neprilysin activity (CSF-NEP) in patients with AD-converted mild cognitive impairment and early AD as compared with age-matched control subjects. The altered CSF-NEP likely reflects changes in neuronal neprilysin, since transfer of neprilysin from brain tissue into CSF was demonstrated by injecting neprilysin-carrying viral vector into the brains of neprilysin-deficient mice. Interestingly, CSF-NEP showed an elevation with the progression of AD. Along with a close association of CSF-NEP with CSF tau proteins, this finding suggests that presynaptically located neprilysin can be released into CSF as a consequence of synaptic disruption. The impact of neuronal damages on CSF-NEP was further demonstrated by a prominent increase of CSF-NEP in rats exhibiting kainate-induced neurodegeneration. Our results unequivocally indicate significance of CSF-NEP as a biochemical indicator to pursue a pathological process that involves decreased neprilysin activity and A beta-induced synaptic toxicity, and the support the potential benefits of neprilysin up-regulation in ameliorating neuropathology in prodromal and early AD.

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PubMed2005

The relationship between body mass index and a plasma lipid peroxidation biomarker in an older, healthy Asian community.

PURPOSE: To examine the association between body mass index (BMI) and the plasma level of a lipid peroxidation biomarker in a large sample of elderly healthy Asian population. This cross-sectional study included 1150 community-dwelling Japanese aged 70 years or older in 2002. METHODS: We measured the lipid peroxidation biomarker 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) using the ELISA method. We also measured the weight and height and calculated the BMI as weight (kg)/height (m)2. RESULTS: After adjustment for potential confounders, the mean +/- SE plasma 8-iso-PGF(2alpha) level was significantly higher in subjects with higher BMI: 21.1 +/- 0.8 pg/ml in those with BMI of 30.0 or more; 20.5 +/- 0.3 pg/ml in those with BMI between 25.0 and 29.9; 20.0 +/- 0.2 pg/ml in those with BMI between 18.5 and 24.9; and 19.0 +/- 0.7 pg/ml in those with BMI of less than 18.5 (p for trend = 0.011). CONCLUSIONS: Our results demonstrated that in the healthy Asian population, there was a modest but significant relationship between BMI and the plasma lipid peroxidation level.

Aged↗
PubMed2005

Plasma homocysteine and risk of coexisting silent brain infarction in Alzheimer's disease.

BACKGROUND: Cerebrovascular disease is common in Alzheimer's disease (AD). Elevated plasma homocysteine (pHcy) levels are reported to be associated with an increased risk of poor cognition and dementia. OBJECTIVE: To determine whether high pHcy levels are associated with an increased risk of coexisting silent brain infarctions (SBIs) in AD. METHODS: Study population comprising 143 outpatients with clinical diagnosis of probable AD (73.3 +/- 7.0 years) were classified into 2 groups according to the presence or absence of SBIs on magnetic resonance imaging. RESULTS: SBIs were noted in 32.9% (47/143) of the AD patients. The pHcy levels in the AD with SBIs (14.0 +/- 4.5 micromol/l) were significant ly elevated compared with the AD without SBIs (11.7 +/- 4.7 micromol/l, p = 0.007). After adjusting for age and gender, high pHcy (>12.4 micromol/l), but not hypertension, was associated with an increased risk of developing SBIs in AD (OR = 4.61, 95% CI = 1.74-12.2, p = 0.002). However, age at onset, cognitive function, cerebrospinal tau or amyloid beta-peptide(1-42) levels were not significantly correlated with pHcy levels in AD. CONCLUSION: SBIs commonly coexist with AD, and may be a unique vascular condition in which homocysteine plays an important role. Homocysteine-lowering therapy rather than antihypertensive medication might be an appropriate strategy to prevent stroke associated with AD.

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PubMed2005

Cognitive decline in patients with long-term domiciliary oxygen therapy.

Cognitive and psycho-physiological condition in patients with long-term domiciliary oxygen therapy (DOT) remains uncertain. A cross sectional analysis was performed to investigate the age-related changes in cognitive and psycho-physiologic functions in patients with chronic respiratory failure receiving long-term DOT. Two expert practitioners visited the patient's home and examined them for analysis of cognitive function, emotional status, physical activity and degree of dyspneic sensation. One hundred and thirty-five patients completed the study. Control data from a cohort of 718 community dwellers were also included in this study. Male patients had significantly higher rates of chronic obstructive pulmonary disease (71% vs 47%, p = 0.001), lower values of forced expiratory volume in one second (FEV1.0) % (49.7 +/- 10.3 [standard deviation, S.D.] vs 66.0 +/- 7.5% predicted, p = 0.002) and higher Borg score, an indicator of dyspneic sensation, during daily exercise (3.2 +/- 0.8 [S.D.] vs 1.4 +/- 0.6, p = 0.01) compared with female patients. Linear regression analysis based on mean Mini-Mental State Examination scores, an indicator of cognitive function, showed that age-related cognitive decline was more pronounced in female patients than in female controls (-0.524/year, R2 = 0.426 vs -0.120/year, R2 = 0.027, p < 0.0001), while there was no significant difference between male patients and male controls (-0.156/year, R2 = 0.054, vs -0.077/year, R2 = 0.016, p = 0.231). These results demonstrate that age-related cognitive decline is more exaggerated in female patients receiving long-term DOT which should be taken into consideration in caring for patients with chronic respiratory failure.

Age Factors↗
PubMed2005

Risk of falls in Alzheimer's disease: a prospective study.

OBJECTIVE: Falls are common in patients with Alzheimer's disease (AD). Identification of the potential risk factors and developing preventive strategies for falls will have a significant impact in maintaining the quality of life in AD. PATIENTS: Clinical follow-up of 124 (74.1+/-6.1 years, range 62-88) mild to moderate AD patients in an outpatient memory clinic. METHODS: Postural sway, cognitive function, use of neuroleptics, severity of periventricular and deep white matter lesions, and the presence or absence of silent brain infarctions on magnetic resonance imaging were assessed at baseline. RESULTS: A total of 104 patients (84%) completed the study. Fall events were confirmed in 42.3% (44/104). After adjustment for age, gender, and cognitive status, a high grade of periventricular white matter lesions (odds ratio 8.7 [95%CI 1.5 to 51.8], p = 0.017) and neuroleptic drug use (odds ratio 3.5 [95%CI 1.2 to 10.5], p = 0.027) were significantly associated with an increased risk of falls. CONCLUSION: Our results suggest that periventricular white matter lesions and the use of neuroleptics may be related to falls in mild to moderate AD. A comprehensive risk management of brain ischemia as well as the use of the smallest efficacious dose of neuroleptics in the treatment of behavioral and psychiatric symptoms of AD should be recommended to help reduce the risk of unexpected falls.

Accidental Falls↗
PubMed2004

Cerebrospinal fluid tau protein and periventricular white matter lesions in patients with mild cognitive impairment: implications for 2 major pathways.

BACKGROUND: Mild cognitive impairment (MCI) may be a heterogeneous condition rather than a uniform disease entity. OBJECTIVE: To develop reliable tools that aid in identifying patients at risk of developing Alzheimer disease (AD) among heterogeneous populations with MCI to maximize the benefits of emerging therapies for AD. DESIGN: A 2-year prospective study. SETTING: Clinical follow-up in an outpatient memory clinic. PATIENTS: Seventy-two consecutive older patients with memory complaints. MAIN OUTCOME MEASURES: Cerebrospinal fluid tau levels, severity of periventricular and deep white matter lesions, silent brain infarction on magnetic resonance imaging, plasma homocysteine levels, apolipoprotein E genotype, and other vascular risk factors were assessed at baseline. RESULTS: Fifty-seven patients were diagnosed as having amnestic MCI. Forty-one patients with (AD-converted MCI group) or without (progressive MCI group) conversion to dementia and AD progressed over time, whereas the other 16 patients remained cognitively stable (stable MCI group). The stable MCI group was characterized by normal cerebrospinal fluid tau levels and a high grade of periventricular white matter lesions (PWMLs). The progressive MCI and AD-converted MCI groups had increased cerebrospinal fluid tau levels and low grades of PWMLs. A logistic regression model showed that age was significantly associated with developing PWMLs (P =.03; odds ratio, 1.15; 95% confidence interval, 1.0-1.3). CONCLUSIONS: Tau-related AD pathologic conditions and possibly ischemic PWMLs represent 2 major etiologies in the development of MCI, reflecting heterogeneity in the clinical progression. Because the progressive type of MCI may be a primary target of clinical trials that aim at secondary prevention of dementia, these patients should be identified by appropriate biomarkers and neuroimaging techniques.

Aged↗
PubMed2004

Increased plasma 8-isoprostane levels in hypertensive subjects: the Tsurugaya Project.

To examine the relationship between 8-isoprostane and blood pressure, we measured plasma 8-isoprostane concentration and home blood pressure levels in an elderly Japanese population. Our study population comprised 569 subjects aged 70 years and over who were not receiving antihypertensive medication. On the basis of their blood pressure values, the participants were classified into three groups: normotensive (home blood pressure <135/85 mmHg), hypertensive (home blood pressure 135/85-160/90 mmHg), and severely hypertensive (home blood pressure > or =160/90 mmHg). The mean plasma 8-isoprostane level in the severely hypertensive group (21.1+/-5.2 pg/ml) was significantly higher than that in the normotensive (20.2+/-4.9 pg/ml) or hypertensive (19.7+/-5.1 pg/ml) group, and this result was unchanged when we adjusted for possible confounding factors such as age, sex, use of vitamin A, C or E supplements, smoking status, drinking status, body mass index, use of non-steroidal anti-inflammatory drugs, history of diabetes, hypercholesterolemia, home heart rate and serum creatinine level. Thus, the level of plasma 8-isoprostane appears to be elevated in older subjects with severe hypertension.

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PubMed2004

C-reactive protein and peripheral artery disease among Japanese elderly: the Tsurugaya Project.

We investigated the cross-sectional relationship between ankle brachial index and cardiovascular disease risk factors, including C-reactive protein (CRP), among Japanese elderly, a topic which has had little prior epidemiologic study. Our study population comprised 946 subjects aged at least 70 years in whom both CRP and ankle brachial index were measured. The participants were classified into a low (ankle brachial index<0.9) and normal ankle brachial index group. We found that current smoking, high-density lipoprotein cholesterol <40 mg/dl, a low body mass index (continuous variable), hypertension, diabetes and statin use were all significantly related to a lower ankle brachial index. Higher log-transformed CRP level was significantly related to a lower ankle brachial index after adjustment for the cardiovascular risk factors mentioned above (p <0.01). The odds ratios for low ankle brachial index compared to 0-1 risk factors were 5.79 (95% confidence interval [CI]: 2.99-11.20) for 2 risk factors and 17.45 (95% CI: 6.78-49.91) for 3 or more risk factors; independently of other risk factors, the odds ratio for CRP>1.0 mg/l was 2.10 (95% CI: 1.13-3.88) compared to lower CRP values. Thus, a high level of CRP is related to a low ankle brachial index among Japanese elderly as well as Western subjects. This is the first study to report the relationship between CRP and low ankle brachial index among Japanese elderly.

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