한국의 알츠하이머병 환자에서 아세틸콜린 에스터레이스 억제제의 뇌척수액 베타아밀로이드 1-42 분획과 인산화타우단백 농도에 미치는 효과
The Effect of Acetylcholine Esterase Inhibitor on Cerebrospinal Fluid β-Amyloid 1-42 and Phosphorylated Tau Protein in Korean Alzheimer’s Disease Patients: Preliminary Study
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Background: Alzheimer’s disease (AD) is characterized by the pathology of amyloid plaques and tau-associated neurofibrillary tangles. Acetylcholine esterase (AChE) transforms the β-amyloid monomer into an oligomer, and increases β-amyloid aggregation in the brain. Increased β-amyloid breaks the cytoskeleton of the brain by hyperphosphorylation of the tau protein. Previous studies support that AChE inhibitor has an inhibitory effect on toxicity of the β-amyloid and phophorylated tau protein. The purpose of this study was to analyze the CSF β-amyloid 1-42 (Aβ1-42) and phosphorylated tau protein in AD and determine their difference depending on whether AChE inhibitor was taken or not. Methods: Subjects included 16 AD, 14 normal controls, and 15 disease controls. Nine of AD group had taken an AChE inhibitor while the remainder had not. The CSF Aβ1-42 and phosphorylated tau were measured by ELISA. Results: The CSF Aβ1-42 levels were lower in AD patients than in other groups (p<0.01). We also found increased CSF Aβ1-42 levels in the AChE inhibitor users, compared with non-users. Conclusions: The level of CSF Aβ1-42 may have a diagnostic value in the patients with cognitive impairments. Also, we may expect the effect of AChE inhibitor on Alzheimer’s pathology by measuring CSF Aβ1-42 levels. Therefore, the level of CSF Aβ1-42 may serve as a biological surrogate marker for AD treatment.
Abstract
Background: Alzheimer’s disease (AD) is characterized by the pathology of amyloid plaques and tau-associated neurofibrillary tangles. Acetylcholine esterase (AChE) transforms the β-amyloid monomer into an oligomer, and increases β-amyloid aggregation in the brain. Increased β-amyloid breaks the cytoskeleton of the brain by hyperphosphorylation of the tau protein. Previous studies support that AChE inhibitor has an inhibitory effect on toxicity of the β-amyloid and phophorylated tau protein. The purpose of this study was to analyze the CSF β-amyloid 1-42 (Aβ1-42) and phosphorylated tau protein in AD and determine their difference depending on whether AChE inhibitor was taken or not. Methods: Subjects included 16 AD, 14 normal controls, and 15 disease controls. Nine of AD group had taken an AChE inhibitor while the remainder had not. The CSF Aβ1-42 and phosphorylated tau were measured by ELISA. Results: The CSF Aβ1-42 levels were lower in AD patients than in other groups (p<0.01). We also found increased CSF Aβ1-42 levels in the AChE inhibitor users, compared with non-users. Conclusions: The level of CSF Aβ1-42 may have a diagnostic value in the patients with cognitive impairments. Also, we may expect the effect of AChE inhibitor on Alzheimer’s pathology by measuring CSF Aβ1-42 levels. Therefore, the level of CSF Aβ1-42 may serve as a biological surrogate marker for AD treatment.
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