Borroni B, Colciaghi F, Pastorino L, Pettenati C, Cottini E, Rozzini L, Monastero R, Lenzi G L, Cattabeni F, Di Luca M, Padovani A
Department of Neurology, University of Brescia, Italy.
Arch Neurol. 2001 Mar;58(3):442-6. doi: 10.1001/archneur.58.3.442.
Amyloid precursor protein (APP) forms with apparent molecular weights of 130, 110, and 106 kd are present in human platelets. It has been demonstrated that Alzheimer disease (AD) is specifically associated with a decreased APP forms ratio in platelets.
To investigate whether acetylcholinesterase (AChE) inhibitor treatment modifies the ratio of platelet APP forms in patients with AD.
From a large sample of patients with probable AD, 30 with mild to moderate AD were selected. Each patient underwent a clinical evaluation including the Mini-Mental State Examination (MMSE) and platelet APP forms analysis at baseline and after 30 days. During this interval, 20 of 30 patients with AD were treated with donepezil hydrochloride (5 mg/d), a piperidine phosphate-based cholinesterase inhibitor. Platelets were subjected to Western blot analysis using monoclonal antibody (22C11). The ratio between the immunoreactivity of the higher-molecular-weight APP form (130 kd) and the lower forms (106 and 110 kd) was measured.
All patients taking donepezil completed the 30 days of treatment without adverse effects. The platelet APP forms ratio at baseline did not differ between the 2 AD groups (mean +/- SD optical density ratio: untreated AD, 0.47 +/- 0.12; treated AD, 0.38 +/- 0.18), whereas a significant difference was found at follow-up (mean +/- SD optical density ratio: untreated AD, 0.45 +/- 0.17; treated AD, 0.77 +/- 0.29; P<.001). A significant improvement in MMSE scores in treated AD patients was observed from baseline (16.9 +/- 3.8) to 30 days (18.9 +/- 4.42) (P<.009, 30 days vs baseline), but no significant correlation was found in treated AD patients between MMSE score improvement and APP forms/ratio increase (P =.09).
Administration of AChE inhibitors increases the ratio of APP forms in platelets of patients with AD, suggesting a potential effect of AChE inhibitors on APP trafficking or processing in a peripheral cell.
人血小板中存在表观分子量为130、110和106kd的淀粉样前体蛋白（APP）形式。已证实阿尔茨海默病（AD）与血小板中APP形式比例降低存在特异性关联。
研究乙酰胆碱酯酶（AChE）抑制剂治疗是否会改变AD患者血小板APP形式的比例。
从大量可能患有AD的患者样本中，选取30例轻度至中度AD患者。每位患者在基线时和30天后均接受了包括简易精神状态检查表（MMSE）和血小板APP形式分析在内的临床评估。在此期间，30例AD患者中有20例接受了盐酸多奈哌齐（5mg/d）治疗，盐酸多奈哌齐是一种基于哌啶磷酸盐的胆碱酯酶抑制剂。使用单克隆抗体（22C11）对血小板进行蛋白质印迹分析。测量高分子量APP形式（130kd）与低分子量形式（106和110kd）的免疫反应性之间的比例。
所有服用多奈哌齐的患者均完成了30天的治疗，且无不良反应。两个AD组在基线时的血小板APP形式比例无差异（平均±标准差光密度比值：未治疗的AD组，0.47±0.12；治疗的AD组，0.38±0.18），而在随访时发现有显著差异（平均±标准差光密度比值：未治疗的AD组，0.45±0.17；治疗的AD组，0.77±0.29；P<0.001）。观察到治疗的AD患者的MMSE评分从基线时的（16.9±3.8）显著改善至30天时的（18.9±4.42）（P<0.009，30天与基线相比），但在治疗的AD患者中，MMSE评分改善与APP形式/比例增加之间未发现显著相关性（P = 0.09）。
给予AChE抑制剂可增加AD患者血小板中APP形式的比例，提示AChE抑制剂对外周细胞中APP的运输或加工可能具有潜在作用。
