1998 Fiscal Year Final Research Report Summary
A STUDY OF CENTRAL CHOLINERGIC SYSTEMS IN DEMEMTIA
| Project/Area Number |
09670639
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
SHINOTO Hitoshi CHIBA UNIVERSITY,DEPARTMENT OF NEUROLOGY,LECTURER, 医学部, 講師 (90226150)
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| Co-Investigator(Kenkyū-buntansha) |
IRIE Toshiaki NATIONAL INSTITUTE OF RADIOLOGICAL SCIENCES,DIVISION OF ADVANCED MEDICAL IMAGING, 高度診断機能研究ステーション, ユニットリーダー (40160072)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Alzheimer's disease / acetylcholine / positron emission tomography / acetycholinesterase / Parkinson's disease |
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| Research Abstract |
We have developed a method to measure acetylcholinesterase (AChE) activity, a marker of cholinergic neuronal function, in the brain by positron emission tomography (PET). An analog of acetyIcholine, N-methyl-4-piperidyl acetate (MP4A), was labeled with carbon-11, and brain AChE activity was measured quantitatively using [^<11>C]MP4A.A three-compartment model was applied to calculate regional brain AChE activity using metabolite corrected arterial plasma input function. In Alzheimer's disease (n=19), there was a significant reduction (-24%) of AChE activity in the cerebral cortex, amygdala, and hippocampus compared with age-matched normal controls (n=14). There was a significant inverse correlation between cortical AChE activity and severity of dementia in Alzheimer's disease, supporting cholinergic hypothesis of dementia in Alzheimer's disease. No age effect was seen in normal controls (n=23) ranging in age 24 to 89 years. The results suggest that Alzheimer's disease is not an exaggerated form of normal aging. In Parkinson's disease (n=16), AChE activity in the cerebral cortex and thalamus was often reduced, especially in advanced and demented patients. In progressive supranuclear palsy (PSP : n=12), there was a marked reduction of AChE activity in the thalamus, suggesting that there was a preferential loss of cholinergic system in the brainstem. When the thalamic to cerebral cortical AChE actitity ratio was taken for each subject, Parkinson's disease and PSP were separated, suggesting that PET measurement of AChE activity may be useful for differentiating the two similar disorders.
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[Publications] Iyo, M., Namba, H., Fukushi, K., Shinotoh, H., Nagatsuka, S., Suhara, T., Sudo, Y., Suzuki, K., Irie, T.: "In vivo measurement using PET of acetylcholinesterase activity in the brains of patients with Alzheimer's disease and normal controls." Lancet. 349. 1805-1809 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Namba, H., Iyo, M., Fukushi, K., Shinotoh, H., Nagatsuka, S., Suhara, T., Sudo, Y., Suzuki, K., Irie, T.: "Human brain acetylcholinesterase activity measured by positron emission tomography.-procedure, normal values, and effect of age." Eur J Nucl Med. (in press).
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「研究成果報告書概要(欧文)」より
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[Publications] Shinotoh, H., Namba, H., Yamaguchi, M., Fukushi, K., Nagatsuka, S., Iyo, M., Asahina, M., Hattori, T., Tanada, S,Irie, T.: "PET measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson's disease and progressive supranuclear palsy." Ann Neurol. (in press).
Description
「研究成果報告書概要(欧文)」より
