Ota T

References (26)

Title : New Series of Zaxinone Mimics (MiZax) for Fundamental and Applied Research - Jamil_2023_Biomolecules_13_
Author(s) : Jamil M , Lin PY , Berqdar L , Wang JY , Takahashi I , Ota T , Alhammad N , Chen GE , Asami T , Al-Babili S
Ref : Biomolecules , 13 : , 2023
Abstract : The apocarotenoid zaxinone is a recently discovered regulatory metabolite required for proper rice growth and development. In addition, zaxinone and its two mimics (MiZax3 and MiZax5) were shown to have a remarkable growth-promoting activity on crops and a capability to reduce infestation by the root parasitic plant Striga through decreasing strigolactone (SL) production, suggesting their potential for application in agriculture and horticulture. In the present study, we developed a new series of MiZax via structural modification of the two potent zaxinone mimics (MiZax3 and MiZax5) and evaluated their effect on plant growth and Striga infestation. In general, the structural modifications to MiZax3 and MiZax5 did not additionally improve their overall performance but caused an increase in certain activities. In conclusion, MiZax5 and especially MiZax3 remain the likely most efficient zaxinone mimics for controlling Striga infestation.
ESTHER : Jamil_2023_Biomolecules_13_
PubMedSearch : Jamil_2023_Biomolecules_13_
PubMedID: 37627271

Title : Zaxinone mimics (MiZax) efficiently promote growth and production of potato and strawberry plants under desert climate conditions - Wang_2023_Sci.Rep_13_17438
Author(s) : Wang JY , Jamil M , AlOtaibi TS , Abdelaziz ME , Ota T , Ibrahim OH , Berqdar L , Asami T , Ahmed Mousa MA , Al-Babili S
Ref : Sci Rep , 13 :17438 , 2023
Abstract : Climate changes and the rapid expanding human population have become critical concerns for global food security. One of the promising solutions is the employment of plant growth regulators (PGRs) for increasing crop yield and overcoming adverse growth conditions, such as desert climate. Recently, the apocarotenoid zaxinone and its two mimics (MiZax3 and MiZax5) have shown a promising growth-promoting activity in cereals and vegetable crops under greenhouse and field conditions. Herein, we further investigated the effect of MiZax3 and MiZax5, at different concentrations (5 and 10 microM in 2021; 2.5 and 5 microM in 2022), on the growth and yield of the two valuable vegetable crops, potato and strawberry, in the Kingdom of Saudi of Arabia. Application of both MiZax significantly increased plant agronomic traits, yield components and total yield, in five independent field trials from 2021 to 2022. Remarkably, the amount of applied MiZax was far less than humic acid, a widely applied commercial compound used here for comparison. Hence, our results indicate that MiZax are very promising PGRs that can be applied to promote the growth and yield of vegetable crops even under desert conditions and at relatively low concentrations.
ESTHER : Wang_2023_Sci.Rep_13_17438
PubMedSearch : Wang_2023_Sci.Rep_13_17438
PubMedID: 37838798

Title : Rational design of Striga hermonthica-specific seed germination inhibitors - Zarban_2022_Plant.Physiol_188_1369
Author(s) : Zarban RA , Hameed UFS , Jamil M , Ota T , Wang JY , Arold ST , Asami T , Al-Babili S
Ref : Plant Physiol , 188 :1369 , 2022
Abstract : The obligate hemiparasitic weed Striga hermonthica grows on cereal roots and presents a severe threat to global food security by causing enormous yield losses, particularly in sub-Saharan Africa. The rapidly increasing Striga seed bank in infested soils provides a major obstacle in controlling this weed. Striga seeds require host-derived strigolactones (SLs) for germination, and corresponding antagonists could be used as germination inhibitors. Recently, we demonstrated that the common detergent Triton X-100 is a specific inhibitor of Striga seed germination by binding noncovalently to its receptor, S. hermonthica HYPO-SENSITIVE TO LIGHT 7 (ShHTL7), without blocking the rice (Oryza sativa) SL receptor DWARF14 (OsD14). Moreover, triazole ureas, the potent covalently binding antagonists of rice SL perception with much higher activity toward OsD14, showed inhibition of Striga but were less specific. Considering that Triton X-100 is not suitable for field application and by combining structural elements of Triton and triazole urea, we developed two hybrid compounds, KK023-N1 and KK023-N2, as potential Striga-specific germination inhibitors. Both compounds blocked the hydrolysis activity of ShHTL7 but did not affect that of OsD14. Binding of KK023-N1 diminished ShHTL7 interaction with S. hermonthica MORE AXILLARY BRANCHING 2, a major component in SL signal transduction, and increased ShHTL7 thermal specificity. Docking studies indicate that KK023-N1 binding is not covalent but is caused by hydrophobic interactions. Finally, in vitro and greenhouse tests revealed specific inhibition of Striga seed germination, which led to a 38% reduction in Striga infestation in pot experiments. These findings reveal that KK023-N1 is a potential candidate for combating Striga and a promising basis for rational design and development of further Striga-specific herbicides.
ESTHER : Zarban_2022_Plant.Physiol_188_1369
PubMedSearch : Zarban_2022_Plant.Physiol_188_1369
PubMedID: 34850204
Gene_locus related to this paper: strhe-ShHTL7

Title : Evaluation of the Biostimulant Activity of Zaxinone Mimics (MiZax) in Crop Plants - Wang_2022_Front.Plant.Sci_13_874858
Author(s) : Wang JY , Jamil M , Hossain MG , Chen GE , Berqdar L , Ota T , Blilou I , Asami T , Al-Solimani SJ , Mousa MAA , Al-Babili S
Ref : Front Plant Sci , 13 :874858 , 2022
Abstract : Global food security is a critical concern that needs practical solutions to feed the expanding human population. A promising approach is the employment of biostimulants to increase crop production. Biostimulants include compounds that boost plant growth. Recently, mimics of zaxinone (MiZax) were shown to have a promising growth-promoting effect in rice (Oryza sativa). In this study, we investigated the effect of MiZax on the growth and yield of three dicot horticultural plants, namely, tomato (Solanum lycopersicum), capsicum (Capsicum annuum), and squash (Cucurbita pepo) in different growth environments, as well as on the growth and development of the monocot date palm (Phoenix dactylifera), an important crop in the Middle East. The application of MiZax significantly enhanced plant height, flower, and branch numbers, fruit size, and total fruit yield in independent field trials from 2020 to 2021. Importantly, the amount of applied MiZax was far less than that used with the commercial compound humic acid, a widely used biostimulant in horticulture. Our results indicate that MiZax have significant application potential to improve the performance and productivity of horticultural crops.
ESTHER : Wang_2022_Front.Plant.Sci_13_874858
PubMedSearch : Wang_2022_Front.Plant.Sci_13_874858
PubMedID: 35783933

Title : Function of hydroxycinnamoyl spermidines in seedling growth of Arabidopsis - Takahashi_2022_Biosci.Biotechnol.Biochem_86_294
Author(s) : Takahashi I , Ota T , Asami T
Ref : Biosci Biotechnol Biochem , 86 :294 , 2022
Abstract : Hydroxycinnamic acid amides are involved in various developmental processes as well as in biotic and abiotic stress responses. Among them, the presence of spermidine derivatives, such as N1,N8-di(coumaroyl)-spermidine and N1,N8-di(sinapoyl)-spermidine, and their biosynthetic genes have been reported in Arabidopsis, but their functions in plants are still unknown. We chemically synthesized the above-mentioned spermidine derivatives to assess their physiological functions in Arabidopsis. We evaluated the growth and development of chemically treated Arabidopsis and demonstrated that these compounds inhibited seed germination, hypocotyl elongation, and primary root growth, which could be due to modulation of plant hormone homeostasis and signaling. The results suggest that these compounds are regulatory metabolites that modulate plant growth and development.
ESTHER : Takahashi_2022_Biosci.Biotechnol.Biochem_86_294
PubMedSearch : Takahashi_2022_Biosci.Biotechnol.Biochem_86_294
PubMedID: 34958361

Title : Striga hermonthica Suicidal Germination Activity of Potent Strigolactone Analogs: Evaluation from Laboratory Bioassays to Field Trials - Jamil_2022_Plants.(Basel)_11__
Author(s) : Jamil M , Wang JY , Yonli D , Ota T , Berqdar L , Traore H , Margueritte O , Zwanenburg B , Asami T , Al-Babili S
Ref : Plants (Basel) , 11 : , 2022
Abstract : The obligate hemiparasite Striga hermonthica is one of the major global biotic threats to agriculture in sub-Saharan Africa, causing severe yield losses of cereals. The germination of Striga seeds relies on host-released signaling molecules, mainly strigolactones (SLs). This dependency opens up the possibility of deploying SL analogs as "suicidal germination agents" to reduce the accumulated seed bank of Striga in infested soils. Although several synthetic SL analogs have been developed for this purpose, the utility of these compounds in realizing the suicidal germination strategy for combating Striga is still largely unknown. Here, we evaluated the efficacy of three potent SL analogs (MP3, MP16, and Nijmegen-1) under laboratory, greenhouse, and farmer's field conditions. All investigated analogs showed around a 50% Striga germination rate, equivalent to a 50% reduction in infestation, which was comparable to the standard SL analog GR24. Importantly, MP16 had the maximum reduction of Striga emergence (97%) in the greenhouse experiment, while Nijmegen-1 appeared to be a promising candidate under field conditions, with a 43% and 60% reduction of Striga emergence in pearl millet and sorghum fields, respectively. These findings confirm that the selected SL analogs appear to make promising candidates as simple suicidal agents both under laboratory and real African field conditions, which may support us to improve suicidal germination technology to deplete the Striga seed bank in African agriculture.
ESTHER : Jamil_2022_Plants.(Basel)_11__
PubMedSearch : Jamil_2022_Plants.(Basel)_11__
PubMedID: 35448773

Title : Efficient Mimics for Elucidating Zaxinone Biology and Promoting Agricultural Applications - Wang_2020_Mol.Plant_13_1654
Author(s) : Wang JY , Jamil M , Lin PY , Ota T , Fiorilli V , Novero M , Zarban RA , Kountche BA , Takahashi I , Martinez C , Lanfranco L , Bonfante P , de Lera AR , Asami T , Al-Babili S
Ref : Mol Plant , 13 :1654 , 2020
Abstract : Zaxinone is an apocarotenoid regulatory metabolite required for normal rice growth and development. In addition, zaxinone has a large application potential in agriculture, due to its growth-promoting activity and capability to alleviate infestation by the root parasitic plant Striga through decreasing strigolactone (SL) production. However, zaxinone is poorly accessible to the scientific community because of its laborious organic synthesis that impedes its further investigation and utilization. In this study, we developed easy-to-synthesize and highly efficient mimics of zaxinone (MiZax). We performed a structure-activity relationship study using a series of apocarotenoids distinguished from zaxinone by different structural features. Using the obtained results, we designed several phenyl-based compounds synthesized with a high-yield through a simple method. Activity tests showed that MiZax3 and MiZax5 exert zaxinone activity in rescuing root growth of a zaxinone-deficient rice mutant, promoting growth, and reducing SL content in roots and root exudates of wild-type plants. Moreover, these compounds were at least as efficient as zaxinone in suppressing transcript level of SL biosynthesis genes and in alleviating Striga infestation under greenhouse conditions, and did not negatively impact mycorrhization. Taken together, MiZax are a promising tool for elucidating zaxinone biology and investigating rice development, and suitable candidates for combating Striga and increasing crop growth.
ESTHER : Wang_2020_Mol.Plant_13_1654
PubMedSearch : Wang_2020_Mol.Plant_13_1654
PubMedID: 32835886

Title : A New Series of Carlactonoic Acid Based Strigolactone Analogs for Fundamental and Applied Research - Jamil_2020_Front.Plant.Sci_11_434
Author(s) : Jamil M , Kountche BA , Wang JY , Haider I , Jia KP , Takahashi I , Ota T , Asami T , Al-Babili S
Ref : Front Plant Sci , 11 :434 , 2020
Abstract : Strigolactones (SLs) are a group of carotenoid derived plant hormones that play a key role in establishing plant architecture and adapting it to environmental changes, and are involved in plants response to biotic and abiotic stress. SLs are also released into the soil to serve as a chemical signal attracting beneficial mycorrhizal fungi. However, this signal also induces seed germination in root parasitic weeds that represent a major global threat for agriculture. This wide spectrum of biological functions has made SL research one of the most important current topics in fundamental and applied plant science. The availability of SLs is crucial for investigating SL biology as well as for agricultural application. However, natural SLs are produced in very low amounts, and their organic synthesis is quite difficult, which creates a need for efficient and easy-to-synthesize analogs and mimics. Recently, we have generated a set of SL analogs, Methyl Phenlactonoates (MPs), which resemble the non-canonical SL carlactonoic acid. In this paper, we describe the development and characterization of a new series of easy-to-synthesize MPs. The new analogs were assessed with respect to regulation of shoot branching, impact on leaf senescence, and induction of seed germination in different root parasitic plants species. Some of the new analogs showed higher efficiency in inhibiting shoot branching as well as in triggering parasitic seed germination, compared to the commonly used GR24. MP16 was the most outstanding analog showing high activity in different SL biological functions. In summary, our new analogs series contains very promising candidates for different applications, which include the usage in studies for understanding different aspects of SL biology as well as large scale field application for combating root parasitic weeds, such as Striga hermonthica that devastates cereal yields in sub-Saharan Africa.
ESTHER : Jamil_2020_Front.Plant.Sci_11_434
PubMedSearch : Jamil_2020_Front.Plant.Sci_11_434
PubMedID: 32373143

Title : Methylation at the C-3' in D-Ring of Strigolactone Analogs Reduces Biological Activity in Root Parasitic Plants and Rice - Jamil_2019_Front.Plant.Sci_10_353
Author(s) : Jamil M , Kountche BA , Haider I , Wang JY , Aldossary F , Zarban RA , Jia KP , Yonli D , Shahul Hameed UF , Takahashi I , Ota T , Arold ST , Asami T , Al-Babili S
Ref : Front Plant Sci , 10 :353 , 2019
Abstract : Strigolactones (SLs) regulate plant development and induce seed germination in obligate root parasitic weeds, e.g. Striga spp. Because organic synthesis of natural SLs is laborious, there is a large need for easy-to-synthesize and efficient analogs. Here, we investigated the effect of a structural modification of the D-ring, a conserved structural element in SLs. We synthesized and investigated the activity of two analogs, MP13 and MP26, which differ from previously published AR8 and AR36 only in the absence of methylation at C-3'. The de-methylated MP13 and MP26 were much more efficient in regulating plant development and inducing Striga seed germination, compared with AR8. Hydrolysis assays performed with purified Striga SL receptor and docking of AR8 and MP13 to the corresponding active site confirmed and explained the higher activity. Field trials performed in a naturally Striga-infested African farmer's field unraveled MP13 as a promising candidate for combating Striga by inducing germination in host's absence. Our findings demonstrate that methylation of the C-3' in D-ring in SL analogs has a negative impact on their activity and identify MP13 and, particularly, MP26 as potent SL analogs with simple structures, which can be employed to control Striga, a major threat to global food security.
ESTHER : Jamil_2019_Front.Plant.Sci_10_353
PubMedSearch : Jamil_2019_Front.Plant.Sci_10_353
PubMedID: 31001294

Title : Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease - Hirano_2018_J.Alzheimers.Dis_62_1539
Author(s) : Hirano S , Shinotoh H , Shimada H , Ota T , Sato K , Tanaka N , Zhang MR , Higuchi M , Fukushi K , Irie T , Kuwabara S , Suhara T
Ref : J Alzheimers Dis , 62 :1539 , 2018
Abstract : BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by chronic progressive cognitive decline and displays underlying brain cholinergic dysfunction, providing a rationale for treatment with cholinomimetic medication. The clinical presentations and courses of AD patients may differ by age of onset. OBJECTIVE: The objective of the present study was to illustrate the regional differences of brain acetylcholinesterase (AChE) activity as quantified by N-[11C]methylpiperidinyl-4-acetate ([11C]MP4A) and PET using parametric whole brain analysis and clarify those differences as a function of age. METHODS: 22 early onset AD (EOAD) with age at onset under 65, the remaining 26 as late onset AD (LOAD), and 16 healthy controls (HC) were enrolled. Voxel-based AChE activity estimation of [11C]MP4A PET images was conducted by arterial input and unconstrained nonlinear least-squares method with subsequent parametrical analyses. Statistical threshold was set as Family Wise Error corrected, p-value <0.05 on cluster-level and cluster extent over 30 voxels. RESULTS: Voxel-based group comparison showed that, compared to HC, both EOAD and LOAD showed cortical AChE decrement in parietal, temporal, and occipital cortices, with wider and stringent cortical involvement in the EOAD group, most prominently demonstrated in the temporal region. There was no significant correlation between age and regional cerebral AChE activity except for a small left superior temporal region in the AD group (Brodmann's area 22, Zmax = 5.13, 396 voxels), whereas no significant cluster was found in the HC counterpart. CONCLUSION: Difference in cortical cholinergic dysfunction between EOAD and LOAD may shed some light on the cholinomimetic drug efficacy in AD.
ESTHER : Hirano_2018_J.Alzheimers.Dis_62_1539
PubMedSearch : Hirano_2018_J.Alzheimers.Dis_62_1539
PubMedID: 29562505

Title : Dementia with Lewy bodies can be well-differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity-a [(11) C]MP4A PET study - Shimada_2015_Int.J.Geriatr.Psychiatry_30_1105
Author(s) : Shimada H , Hirano S , Sinotoh H , Ota T , Tanaka N , Sato K , Yamada M , Fukushi K , Irie T , Zhang MR , Higuchi M , Kuwabara S , Suhara T
Ref : Int J Geriatr Psychiatry , 30 :1105 , 2015
Abstract : OBJECTIVE: To investigate the diagnostic performance of brain acetylcholinesterase (AChE) activity measurement using N-[(11) C]-methyl-4-piperidyl acetate (MP4A) and PET in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).
METHODS: Participants were 14 DLB patients, 25 AD patients and 18 age-matched healthy controls (HC). All subjects underwent PET scans and MP4A to measure regional brain AChE activity. We performed anatomical standardization of each brain image, and k3 values, an index of AChE activity, in each voxel were estimated by nonlinear least squares analysis. Volumes of interest (VOIs) were identified on parametric k3 images in frontal, temporal, parietal and occipital cortices, and in anterior and posterior cingulate gyri (ACG and PCG). In each VOI, the differential diagnostic performance between AD and DLB of k3 values was assessed by area under the curve (AUC) of the receiver-operating characteristic. Voxel-based statistical analyses were also performed.
RESULTS: Mean cortical AChE activities in AD patients (-8.2% compared with normal mean) and DLB patients (-27.8%) were lower than HCs (p < 0.05, p < 0.001, respectively). There was a significant difference in mean cortical AChE activities between AD and DLB patients (p < 0.001). All regional brain AChE activities of defined VOIs except ACG were able to well discriminate DLB from AD, and notably performance was the most significant in PCG (AUC = 0.989, 95% CI: 0.965-1.000).
CONCLUSIONS: Brain cholinergic deficit is consistently prominent in DLB compared with AD. PET measurement of brain AChE activity may be useful for the differential diagnosis between DLB and AD. Copyright (c) 2015 John Wiley & Sons, Ltd.
ESTHER : Shimada_2015_Int.J.Geriatr.Psychiatry_30_1105
PubMedSearch : Shimada_2015_Int.J.Geriatr.Psychiatry_30_1105
PubMedID: 26280153

Title : Cholinergic imaging in corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia - Hirano_2010_Brain_133_2058
Author(s) : Hirano S , Shinotoh H , Shimada H , Aotsuka A , Tanaka N , Ota T , Sato K , Ito H , Kuwabara S , Fukushi K , Irie T , Suhara T
Ref : Brain , 133 :2058 , 2010
Abstract : Corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia are all part of a disease spectrum that includes common cognitive impairment and movement disorders. The aim of this study was to characterize brain cholinergic deficits in these disorders. We measured brain acetylcholinesterase activity by [11C] N-methylpiperidin-4-yl acetate and positron emission tomography in seven patients with corticobasal syndrome (67.6+/-5.9 years), 12 with progressive supranuclear palsy (68.5+/-4.1 years), eight with frontotemporal dementia (59.8+/-6.9 years) and 16 healthy controls (61.2+/-8.5 years). Two-tissue compartment three-parameter model and non-linear least squares analysis with arterial input function were performed. k3 value, an index of acetylcholinesterase activity, was calculated voxel-by-voxel in the brain of each subject. The k3 images in each disease group were compared with the control group by using Statistical Parametric Mapping 2. Volume of interest analysis was performed on spatially normalized k3 images. The corticobasal syndrome group showed decreased acetylcholinesterase activity (k3 values) in the paracentral region, frontal, parietal and occipital cortices (P<0.05, cluster corrected). The group with progressive supranuclear palsy had reduced acetylcholinesterase activity in the paracentral region and thalamus (P<0.05, cluster corrected). The frontotemporal dementia group showed no significant differences in acetylcholinesterase activity. Volume of interest analysis showed mean cortical acetylcholinesterase activity to be reduced by 17.5% in corticobasal syndrome (P<0.001), 9.4% in progressive supranuclear palsy (P<0.05) and 4.4% in frontotemporal dementia (non-significant), when compared with the control group. Thalamic acetylcholinesterase activity was reduced by 6.4% in corticobasal syndrome (non-significant), 24.0% in progressive supranuclear palsy (P<0.03) and increased by 3.3% in frontotemporal dementia (non-significant). Both corticobasal syndrome and progressive supranuclear palsy showed brain cholinergic deficits, but their distribution differed somewhat. Significant brain cholinergic deficits were not seen in frontotemporal dementia, which may explain the unresponsiveness of this condition to cholinergic modulation therapy.
ESTHER : Hirano_2010_Brain_133_2058
PubMedSearch : Hirano_2010_Brain_133_2058
PubMedID: 20558417

Title : Estimation of plasma IC50 of donepezil for cerebral acetylcholinesterase inhibition in patients with Alzheimer disease using positron emission tomography - Ota_2010_Clin.Neuropharmacol_33_74
Author(s) : Ota T , Shinotoh H , Fukushi K , Kikuchi T , Sato K , Tanaka N , Shimada H , Hirano S , Miyoshi M , Arai H , Suhara T , Irie T
Ref : Clinical Neuropharmacology , 33 :74 , 2010
Abstract : OBJECTIVES: Estimate the value of in vivo plasma IC50 of donepezil, the concentration of donepezil in plasma that inhibits brain acetylcholinesterase (AChE) activity by 50% at the steady-state conditions of donepezil between the plasma and the brain. METHODS: N-[C] methylpiperidin-4-yl acetate ([C]MP4A) positron emission tomography was performed in 16 patients with probable Alzheimer disease (AD) before and during the treatment of donepezil (5 mg/day) with a mean interval of 5.3 months. The plasma IC50 value of donepezil was estimated from plasma donepezil concentrations and cerebral cortical mean AChE inhibition rates measured by positron emission tomography, using one-parameter model. RESULTS: Donepezil reduced AChE activity uniformly in the cerebral cortex compared with the baseline in each AD patient, and the mean reduction rate in the cerebral cortex was 34.6%. The donepezil concentrations in the plasma ranged from 18.5 to 43.9 ng/mL with a mean of 28.9 +/- 7.3 ng/mL. The plasma IC50 value was estimated to be 53.6 +/- 4.0 ng/mL. CONCLUSIONS: Once the plasma IC50 of donepezil is determined, the brain AChE inhibition rate could be estimated from the plasma concentration of donepezil in each subject based on the plasma IC50. Now that the mean donepezil concentrations in the plasma, when the patients took 5 mg/day, remained 28.9 ng/mL, approximately half of the plasma IC50, higher dose of donepezil might provide further benefits for patients with AD. This technique can be also applied to measure the in vivo plasma IC50 of other cholinesterase inhibitors such as rivastigmine and galantamine.
ESTHER : Ota_2010_Clin.Neuropharmacol_33_74
PubMedSearch : Ota_2010_Clin.Neuropharmacol_33_74
PubMedID: 19935404

Title : Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET - Shimada_2009_Neurology_73_273
Author(s) : Shimada H , Hirano S , Shinotoh H , Aotsuka A , Sato K , Tanaka N , Ota T , Asahina M , Fukushi K , Kuwabara S , Hattori T , Suhara T , Irie T
Ref : Neurology , 73 :273 , 2009
Abstract : OBJECTIVE: To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB). METHODS: Participants included 18 patients with PD, 21 patients with PDD/DLB, and 26 healthy controls. The PD group consisted of nine patients with early PD, each with a disease duration of less than 3 years, five of whom were de novo PD patients, and nine patients with advanced PD, each with a disease duration greater than or equal to 3 years. The PDD/DLB group consisted of 10 patients with PDD and 11 patients with DLB. All subjects underwent PET scans with N-[11C]-methyl-4-piperidyl acetate to measure brain acetylcholinesterase (AChE) activity. Brain AChE activity levels were estimated voxel-by-voxel in a three-compartment analysis using the arterial input function, and compared among our subject groups through both voxel-based analysis using the statistical parametric mapping software SPM5 and volume-of-interest analysis. RESULTS: Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = -12%) (false discovery rate-corrected p value <0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = -27%) (p < 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced. CONCLUSIONS: Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies.
ESTHER : Shimada_2009_Neurology_73_273
PubMedSearch : Shimada_2009_Neurology_73_273
PubMedID: 19474411

Title : PET study of brain acetylcholinesterase in cerebellar degenerative disorders - Hirano_2008_Mov.Disord_23_1154
Author(s) : Hirano S , Shinotoh H , Arai K , Aotsuka A , Yasuno F , Tanaka N , Ota T , Sato K , Fukushi K , Tanada S , Hattori T , Irie T
Ref : Movement Disordersord , 23 :1154 , 2008
Abstract : To elucidate characteristic changes of brain acetylcholinesterase (AChE) in cerebellar degenerative disorders. Eight patients with the cerebellar variant of multiple system atrophy (MSA-C), 7 patients with spinocerebellar ataxia type-3 (SCA-3), 3 patients with SCA-6, and 13 healthy age-matched volunteers participated in this study. Brain AChE activity was measured by [(11)C] N-methylpiperidin-4-yl propionate PET in all subjects. Brain AChE activities were significantly decreased in the thalamus (-27%) and the posterior lobe of cerebellar cortex (-36%) in patients with MSA-C and in the thalamus (-23%) in patients with SCA-3 compared with healthy controls (P < 0.01). Thalamic AChE activities of SCA-3 patients were negatively correlated with the unified Parkinson's disease rating scale motor subscore (P < 0.001). AChE activities were not significantly altered in the cerebral cortex in any disease group. Reduction of AChE activities in the thalamus and cerebellum in MSA and in the thalamus in SCA-3 suggest that cholinergic modulating drugs may have a role in the treatment of ataxia and other symptoms in these disorders.
ESTHER : Hirano_2008_Mov.Disord_23_1154
PubMedSearch : Hirano_2008_Mov.Disord_23_1154
PubMedID: 18412283

Title : Brain acetylcholinesterase activity in FTDP-17 studied by PET -
Author(s) : Hirano S , Shinotoh H , Kobayashi T , Tsuboi Y , Wszolek ZK , Aotsuka A , Tanaka N , Ota T , Fukushi K , Tanada S , Irie T
Ref : Neurology , 66 :1276 , 2006
PubMedID: 16636254

Title : Estimation of plasma IC50 of donepezil hydrochloride for brain acetylcholinesterase inhibition in monkey using N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) and PET - Shiraishi_2005_Neuropsychopharmacology_30_2154
Author(s) : Shiraishi T , Kikuchi T , Fukushi K , Shinotoh H , Nagatsuka S , Tanaka N , Ota T , Sato K , Hirano S , Tanada S , Iyo M , Irie T
Ref : Neuropsychopharmacology , 30 :2154 , 2005
Abstract : Donepezil hydrochloride is a potent and selective inhibitor for brain acetylcholinesterase (AChE) and is currently used worldwide for the treatment of Alzheimer's disease. Until now, there is no in vivo study on the relation between the plasma concentration and the brain AChE inhibition. The purpose of this study was to estimate in vivo plasma IC(50) of donepezil in living monkeys by measuring plasma donepezil concentration (LC/MS/MS) and brain AChE activity with positron emission tomography (PET) and N-[(11)C]methylpiperidin-4-yl acetate, which is an acetylcholine analog recently developed by us for quantifying in vivo brain AChE activity. PET scans with donepezil at two doses, 100 microg/kg (donepezil-1; N=5) or 250 microg/kg (donepezil-2; N=5), were performed using the same monkeys at 4-week intervals. Before each PET scan, baseline PET scans (N=10 in total) were performed without donepezil. The plasma donepezil concentrations 14 min after intravenous injection were proportional to the doses, 17.2+/-2.9 ng/ml (donepezil-1) and 44.0+/-5.0 ng/ml (donepezil-2), and the mean AChE inhibitions in four neocortical regions as evaluated by PET were also dose-dependent, 27% (donepezil-1) and 53% (donepezil-2). In IC(50) estimation, measured plasma donepezil concentrations were corrected for the change during PET scan. The IC(50) values (estimate+/-SE) were 42+/-9.0 (ng/ml; donepezil-1), 34+/-3.2 (donepezil-2), and 37+/-4.1 (combined data). The present method may be useful for in vivo evaluation of other AChE inhibitors and novel drugs.
ESTHER : Shiraishi_2005_Neuropsychopharmacology_30_2154
PubMedSearch : Shiraishi_2005_Neuropsychopharmacology_30_2154
PubMedID: 15920507

Title : Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries - Otsuki_2005_DNA.Res_12_117
Author(s) : Otsuki T , Ota T , Nishikawa T , Hayashi K , Suzuki Y , Yamamoto J , Wakamatsu A , Kimura K , Sakamoto K , Hatano N , Kawai Y , Ishii S , Saito K , Kojima S , Sugiyama T , Ono T , Okano K , Yoshikawa Y , Aotsuka S , Sasaki N , Hattori A , Okumura K , Nagai K , Sugano S , Isogai T
Ref : DNA Research , 12 :117 , 2005
Abstract : We have developed an in silico method of selection of human full-length cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. Fullness rates were increased to about 80% by combination of the oligo-capping method and ATGpr, software for prediction of translation start point and the coding potential. Then, using 5'-end single-pass sequences, cDNAs having the signal sequence were selected by PSORT ('signal sequence trap'). We also applied 'secretion or membrane protein-related keyword trap' based on the result of BLAST search against the SWISS-PROT database for the cDNAs which could not be selected by PSORT. Using the above procedures, 789 cDNAs were primarily selected and subjected to full-length sequencing, and 334 of these cDNAs were finally selected as novel. Most of the cDNAs (295 cDNAs: 88.3%) were predicted to encode secretion or membrane proteins. In particular, 165(80.5%) of the 205 cDNAs selected by PSORT were predicted to have signal sequences, while 70 (54.2%) of the 129 cDNAs selected by 'keyword trap' preserved the secretion or membrane protein-related keywords. Many important cDNAs were obtained, including transporters, receptors, and ligands, involved in significant cellular functions. Thus, an efficient method of selecting secretion or membrane protein-encoding cDNAs was developed by combining the above four procedures.
ESTHER : Otsuki_2005_DNA.Res_12_117
PubMedSearch : Otsuki_2005_DNA.Res_12_117
PubMedID: 16303743

Title : Evaluation of simplified kinetic analyses for measurement of brain acetylcholinesterase activity using N-[11C]Methylpiperidin-4-yl propionate and positron emission tomography - Sato_2004_J.Cereb.Blood.Flow.Metab_24_600
Author(s) : Sato K , Fukushi K , Shinotoh H , Nagatsuka S , Tanaka N , Aotsuka A , Ota T , Shiraishi T , Tanada S , Iyo M , Irie T
Ref : Journal of Cerebral Blood Flow & Metabolism , 24 :600 , 2004
Abstract : The applicability of two reference tissue-based analyses without arterial blood sampling for the measurement of brain regional acetylcholinesterase (AChE) activity using N-[11C]methylpiperidin-4-yl propionate ([11C]MP4P) was evaluated in 12 healthy subjects. One was a linear least squares analysis derived from Blomqvist's equation, and the other was the analysis of the ratio of target-tissue radioactivity relative to reference-tissue radioactivity proposed by Herholz and coworkers. The standard compartment analysis using arterial input function provided reliable quantification of k3 (an index of AChE activity) estimates in regions with low (neocortex and hippocampus), moderate (thalamus), and high (cerebellum) AChE activity with a coefficient of variation (COV) of 12% to 19%. However, the precise k3 value in the striatum, where AChE activity is the highest, was not obtained. The striatum was used as a reference because its time-radioactivity curve was proportional to the time integral of the arterial input function. Reliable k3 estimates were also obtained in regions with low-to-moderate AChE activity with a COV of less than 21% by striatal reference analyses, though not obtained in the cerebellum. Shape analysis, the previous method of direct k3 estimation from the shape of time-radioactivity data, gave k3 estimates in the cortex and thalamus with a somewhat larger COV. In comparison with the standard analysis, a moderate overestimation of k3 by 9% to 18% in the linear analysis and a moderate underestimation by 2% to 13% in the Herholz method were observed, which were appropriately explained by the results of computer simulation. In conclusion, simplified kinetic analyses are practical and useful for the routine analysis of clinical [11C]MP4P studies and are nearly as effective as the standard analysis for detecting regions with abnormal AChE activity.
ESTHER : Sato_2004_J.Cereb.Blood.Flow.Metab_24_600
PubMedSearch : Sato_2004_J.Cereb.Blood.Flow.Metab_24_600
PubMedID: 15181367

Title : Complete sequencing and characterization of 21,243 full-length human cDNAs - Ota_2004_Nat.Genet_36_40
Author(s) : Ota T , Suzuki Y , Nishikawa T , Otsuki T , Sugiyama T , Irie R , Wakamatsu A , Hayashi K , Sato H , Nagai K , Kimura K , Makita H , Sekine M , Obayashi M , Nishi T , Shibahara T , Tanaka T , Ishii S , Yamamoto J , Saito K , Kawai Y , Isono Y , Nakamura Y , Nagahari K , Murakami K , Yasuda T , Iwayanagi T , Wagatsuma M , Shiratori A , Sudo H , Hosoiri T , Kaku Y , Kodaira H , Kondo H , Sugawara M , Takahashi M , Kanda K , Yokoi T , Furuya T , Kikkawa E , Omura Y , Abe K , Kamihara K , Katsuta N , Sato K , Tanikawa M , Yamazaki M , Ninomiya K , Ishibashi T , Yamashita H , Murakawa K , Fujimori K , Tanai H , Kimata M , Watanabe M , Hiraoka S , Chiba Y , Ishida S , Ono Y , Takiguchi S , Watanabe S , Yosida M , Hotuta T , Kusano J , Kanehori K , Takahashi-Fujii A , Hara H , Tanase TO , Nomura Y , Togiya S , Komai F , Hara R , Takeuchi K , Arita M , Imose N , Musashino K , Yuuki H , Oshima A , Sasaki N , Aotsuka S , Yoshikawa Y , Matsunawa H , Ichihara T , Shiohata N , Sano S , Moriya S , Momiyama H , Satoh N , Takami S , Terashima Y , Suzuki O , Nakagawa S , Senoh A , Mizoguchi H , Goto Y , Shimizu F , Wakebe H , Hishigaki H , Watanabe T , Sugiyama A , Takemoto M , Kawakami B , Watanabe K , Kumagai A , Itakura S , Fukuzumi Y , Fujimori Y , Komiyama M , Tashiro H , Tanigami A , Fujiwara T , Ono T , Yamada K , Fujii Y , Ozaki K , Hirao M , Ohmori Y , Kawabata A , Hikiji T , Kobatake N , Inagaki H , Ikema Y , Okamoto S , Okitani R , Kawakami T , Noguchi S , Itoh T , Shigeta K , Senba T , Matsumura K , Nakajima Y , Mizuno T , Morinaga M , Sasaki M , Togashi T , Oyama M , Hata H , Komatsu T , Mizushima-Sugano J , Satoh T , Shirai Y , Takahashi Y , Nakagawa K , Okumura K , Nagase T , Nomura N , Kikuchi H , Masuho Y , Yamashita R , Nakai K , Yada T , Ohara O , Isogai T , Sugano S
Ref : Nat Genet , 36 :40 , 2004
Abstract : As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.
ESTHER : Ota_2004_Nat.Genet_36_40
PubMedSearch : Ota_2004_Nat.Genet_36_40
PubMedID: 14702039
Gene_locus related to this paper: human-ABHD1 , human-ABHD4 , human-ABHD12 , human-ABHD16A , human-ACOT1 , human-LDAH , human-ABHD18 , human-CES1 , human-CES4A , human-CES5A , human-CPVL , human-DAGLB , human-EPHX2 , human-KANSL3 , human-LIPA , human-LPL , human-MEST , human-NDRG1 , human-NLGN1 , human-NLGN4X , human-PRCP , human-PRSS16 , human-SERAC1 , human-TMEM53

Title : A simple method for the detection of abnormal brain regions in Alzheimer's disease patients using [11C]MP4A: comparison with [123I]IMP SPECT - Ota_2004_Ann.Nucl.Med_18_187
Author(s) : Ota T , Shinotoh H , Fukushi K , Nagatsuka S , Namba H , Iyo M , Aotsuka A , Tanaka N , Sato K , Shiraishi T , Tanada S , Arai H , Irie T
Ref : Ann Nucl Med , 18 :187 , 2004
Abstract : We have developed a radiolabeled lipophilic acetylcholine analogue, N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) to measure brain acetylcholinesterase (AChE) activity by positron emission tomography (PET) in vivo. Aiming to develop a new SPECT tracer similar to MP4A, we first proposed a simple method for diagnosing Alzheimer's disease (AD) using [11C]MP4A PET. We performed [11C]MP4A PET and N-isopropyl [123I]iodoamphetamine ([123I]IMP) SPECT in 13 patients with AD and in 17 normal controls (NC). We calculated the ratio of radioactivity of the cortical region of interest (ROI) to that of the cerebellum measured with [11C]MP4A PET (MP4A ratio) and the ratio of regional cerebral blood flow (rCBF) to that of the cerebellum measured with [123I]IMP SPECT (IMP ratio). Eleven cortical ROIs were placed in the frontal, sensorimotor, temporal, parietal, and occipital cortices in both hemispheres and in the posterior cingulate cortex, and z-score was calculated in each ROI in patients with AD compared with NC. When the z-score was 2 or more in a ROI, it was defined as a positive ROI. When a patient had 3 or more positive ROIs, the patient was diagnosed as having AD. The reduction in the MP4A ratio was greater than that in the IMP ratio in all cortical ROIs except for in the right parietal cortex and cingulate cortex in patients with AD. MP4A ratio method showed 92% sensitivity and the IMP ratio method 69% sensitivity for the diagnosis of AD. These results encourage us to develop a new SPECT tracer similar to MP4A for the diagnosis of AD.
ESTHER : Ota_2004_Ann.Nucl.Med_18_187
PubMedSearch : Ota_2004_Ann.Nucl.Med_18_187
PubMedID: 15233279

Title : The amygdala and Alzheimer's disease: positron emission tomographic study of the cholinergic system - Shinotoh_2003_Ann.N.Y.Acad.Sci_985_411
Author(s) : Shinotoh H , Fukushi K , Nagatsuka S , Tanaka N , Aotsuka A , Ota T , Namba H , Tanada S , Irie T
Ref : Annals of the New York Academy of Sciences , 985 :411 , 2003
Abstract : The primary transmitter deficit is cholinergic in Alzheimer's disease (AD), and the amygdala receives a major cholinergic projection from the nucleus basalis of Meynert (Ch4), which may play an important role in the retention of affective conditioning and/or memory consolidation. We measured brain acetylcholinesterase (AChE) activity in 54 patients with AD and in 22 normal controls by positron emission tomography and N-[(11)C]methylpiperidin-4-yl acetate to characterize the cholinergic pathology in AD. The k(3) values were calculated as an index of AChE activity in a three-compartment model analysis using the metabolite-corrected arterial input function. The k(3) values were highly significantly reduced by 20% in the cerebral neocortex (P <0.0001 in the two-tailed t test), 14% in the hippocampus (P <0.001), and 33% in the amygdala (P <0.0001) in AD patients compared with normal controls. The k(3) values were significantly correlated with the Mini-Mental State Examination scores in both the cerebral cortex (P <0.001) and the amygdala (P <0.05) in AD patients, supporting the cholinergic hypothesis of cognitive dysfuncion in AD. Further studies are required, however, to elucidate the specific role of the cholinergic deficit in the amygdala in the emotional and behavioral symptoms in AD.
ESTHER : Shinotoh_2003_Ann.N.Y.Acad.Sci_985_411
PubMedSearch : Shinotoh_2003_Ann.N.Y.Acad.Sci_985_411
PubMedID: 12724174

Title : Effect of donepezil on brain acetylcholinesterase activity in patients with AD measured by PET - Shinotoh_2001_Neurology_56_408
Author(s) : Shinotoh H , Aotsuka A , Fukushi K , Nagatsuka S , Tanaka N , Ota T , Tanada S , Irie T
Ref : Neurology , 56 :408 , 2001
Abstract : Acetylcholinesterase (AChE) activities in the brain of three patients with AD were measured once before and once during donepezil treatment (5 mg/d in two patients, 3 mg/d in one patient) using PET and N-[11C]methylpiperidin-4-yl acetate. Donepezil reduced k(3) values, an index of AChE activity, in the cerebral cortex by 39 +/- 5%. All patients showed some degree of symptomatic improvement, and it was concluded that this improvement was likely caused by improved cholinergic activity by inhibition of AChE in the brain.
ESTHER : Shinotoh_2001_Neurology_56_408
PubMedSearch : Shinotoh_2001_Neurology_56_408
PubMedID: 11171913

Title : Positron emission tomographic measurement of brain acetylcholinesterase activity using N-[(11)C]methylpiperidin-4-yl acetate without arterial blood sampling: methodology of shape analysis and its diagnostic power for Alzheimer's disease - Tanaka_2001_J.Cereb.Blood.Flow.Metab_21_295
Author(s) : Tanaka N , Fukushi K , Shinotoh H , Nagatsuka S , Namba H , Iyo M , Aotsuka A , Ota T , Tanada S , Irie T
Ref : Journal of Cerebral Blood Flow & Metabolism , 21 :295 , 2001
Abstract : N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) is a radiotracer that has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET) using a standard compartment model analysis and a metabolite-corrected arterial input function. In the current study, the authors evaluated the applicability of a simple kinetic analysis without blood sampling, namely shape analysis. First, the authors used computer simulations to analyze factors that affect the precision and bias of shape analysis, then optimized the shape analysis procedure for [11C]MP4A. Before shape analysis execution, the later part of dynamic PET data except for the initial 3 minutes were smoothed by fitting to a bi-exponential function followed by linear interpolation of 8 data points between each of adjacent scan frames. Simulations showed that shape analysis yielded estimates of regional metabolic rates of [11C]MP4A by AChE (k3) with acceptable precision and bias in brain regions with low k3 values such as neocortex. Estimates in regions with higher k3 values became progressively more inaccurate. The authors then applied the method to [11C]MP4A PET data in 10 healthy subjects and 20 patients with Alzheimer's disease (AD). There was a highly significant linear correlation in regional k3 estimates between shape and compartment analyses (300 neocortical regions, [shape k3] = 0.93 x [NLS k3], r = 0.89, P < 0.001). Significant reductions in k3 estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral cortices in patients with AD as compared with controls were observed when using shape analysis (P < 0.013, two-tailed t-test), although these reductions (17% to 20%) were somewhat less than those obtained by compartment analysis (22% to 27%). The sensitivity of shape analysis for detecting neocortical regions with abnormally low k3 in the 20 patients with AD (92 out of 200 regions, 46%) also was somewhat less than compartment analysis (136 out of 200 regions, 68%). However, taking its simplicity and noninvasiveness into account, the authors conclude that quantitative measurement of neocortical AChE activity with shape analysis and [11C]MP4A PET is practical and useful for clinical diagnosis of AD.
ESTHER : Tanaka_2001_J.Cereb.Blood.Flow.Metab_21_295
PubMedSearch : Tanaka_2001_J.Cereb.Blood.Flow.Metab_21_295
PubMedID: 11295884

Title : Kinetic analysis of [(11)C]MP4A using a high-radioactivity brain region that represents an integrated input function for measurement of cerebral acetylcholinesterase activity without arterial blood sampling - Nagatsuka_2001_J.Cereb.Blood.Flow.Metab_21_1354
Author(s) : Nagatsuka Si S , Fukushi K , Shinotoh H , Namba H , Iyo M , Tanaka N , Aotsuka A , Ota T , Tanada S , Irie T
Ref : Journal of Cerebral Blood Flow & Metabolism , 21 :1354 , 2001
Abstract : N -[(11)C]methylpiperidin-4-yl acetate ([(11)C]MP4A) is an acetylcholine analog. It has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET). [(11)C]MP4A is specifically hydrolyzed by AChE in the brain to a hydrophilic metabolite, which is irreversibly trapped locally in the brain. The authors propose a new method of kinetic analysis of brain AChE activity by PET without arterial blood sampling, that is, reference tissue-based linear least squares (RLS) analysis. In this method, cerebellum or striatum is used as a reference tissue. These regions, because of their high AChE activity, act as a biologic integrator of plasma input function during PET scanning, when regional metabolic rates of [(11)C]MP4A through AChE (k(3); an AChE index) are calculated by using Blomqvist's linear least squares analysis. Computer simulation studies showed that RLS analysis yielded k(3) with almost the same accuracy as the standard nonlinear least squares (NLS) analysis in brain regions with low (such as neocortex and hippocampus) and moderately high (thalamus) k(3) values. The authors then applied these methods to [(11) C]MP4A PET data in 12 healthy subjects and 26 patients with Alzheimer disease (AD) using the cerebellum as the reference region. There was a highly significant linear correlation in regional k(3) estimates between RLS and NLS analyses (456 cerebral regions, [RLS k(3) ] = 0.98 x [NLS k(3) ], r = 0.92, P < 0.001). Significant reductions were observed in k(3) estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral neocortices (P < 0.001, single-tailed t-test), and hippocampus (P = 0.012) in patients with AD as compared with controls when using RLS analysis. Mean reductions (19.6%) in these 6 regions by RLS were almost the same as those by NLS analysis (20.5%). The sensitivity of RLS analysis for detecting cortical regions with abnormally low k 3 in the 26 patients with AD (138 of 312 regions, 44%) was somewhat less than NLS analysis (52%), but was greater than shape analysis (33%), another method of [(11)C]MP4A kinetic analysis without blood sampling. The authors conclude that RLS analysis is practical and useful for routine analysis of clinical [(11)C]MP4A studies.
ESTHER : Nagatsuka_2001_J.Cereb.Blood.Flow.Metab_21_1354
PubMedSearch : Nagatsuka_2001_J.Cereb.Blood.Flow.Metab_21_1354
PubMedID: 11702050

Title : Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer's disease: a positron emission tomography study - Shinotoh_2000_Ann.Neurol_48_194
Author(s) : Shinotoh H , Namba H , Fukushi K , Nagatsuka S , Tanaka N , Aotsuka A , Ota T , Tanada S , Irie T
Ref : Annals of Neurology , 48 :194 , 2000
Abstract : We measured brain acetylcholinesterase activity in 30 patients with Alzheimer's disease (AD) and 14 age-matched controls by positron emission tomography (PET) and using a carbon 11-labeled acetylcholine analogue. Seven AD patients had repeat PET scans. The k3 values were calculated as an index of acetylcholinesterase activity in a three-compartment analysis using the metabolite corrected arterial input function. Twenty-eight of the 30 AD patients (14 each in the early and late onset subgroups) were retained in the study so as to equalize the range and average severity of cognitive impairment within the early and late onset subgroups. The k3 values were significantly reduced in the neocortex, hippocampus, and amygdala in the early onset AD patients, although the k3 values were significantly reduced only in the temporoparietal cortex and amygdala in the late onset AD patients. In the longitudinal study, all 7 repeat AD patients showed further reduction of cortical k3 values in the second PET scans, with a mean interval of 2 years, suggesting a progressive loss of the ascending cholinergic system from the nucleus basalis of Meynert in AD. In 37 AD patients, there was a highly significant correlation between the cortical k3 values and Mini-Mental State Examination scores, supporting the cholinergic hypothesis in AD.
ESTHER : Shinotoh_2000_Ann.Neurol_48_194
PubMedSearch : Shinotoh_2000_Ann.Neurol_48_194
PubMedID: 10939570