Cattabeni Flaminio, Colciaghi Francesca, Di Luca Monica
Centre of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milano, via Balzaretti 9, 20133, Milano, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2004 Aug;28(5):763-70. doi: 10.1016/j.pnpbp.2004.05.022.
Alzheimer disease (AD) is a progressive neurodegenerative disorder characterised by a progressive cognitive and memory decline. From a neuropathological point of view, Alzheimer disease is defined by the presence of characteristic lesions, i.e. mature senile plaques, neurofibrillary tangles and amyloid angiopathy. In particular, accumulation of the amyloid beta-peptide in the brain parenchyma and vasculature is an invariant event in the pathogenesis of both sporadic and familial Alzheimer cases. Amyloid beta-peptide originates from a larger precursor, the Amyloid Precursor Protein (APP) ubiquitously expressed. Among the different peripheral cells expressing APP forms, platelets are particularly interesting since they show concentrations of its isoforms equivalent to those found in brain. Moreover, a number of laboratories independently described alterations in APP metabolism/concentration in platelets of Alzheimer patients when compared to control subjects matched for demographic characteristics. These observations defined the frame of our work aimed to investigate if a correlation between levels of platelet APP forms and Alzheimer disease could be detected. We have reported that patients affected by Alzheimer disease show a differential level of platelet APP forms. This observation has several implications: APP processing abnormalities, believed to be a very early change in Alzheimer disease in neuronal compartment, does occur in extraneuronal tissues, such as platelets, thus suggesting that Alzheimer disease is a systemic disorder; further, our data strongly indicate that a differential level of platelet APP forms can be considered a potential peripheral marker of Alzheimer disease allowing for discrimination between Alzheimer and other types of dementia with good sensitivity and specificity.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征为进行性认知和记忆衰退。从神经病理学角度来看，阿尔茨海默病由特征性病变的存在来定义，即成熟的老年斑、神经原纤维缠结和淀粉样血管病。特别是，淀粉样β肽在脑实质和血管中的积累是散发性和家族性阿尔茨海默病病例发病机制中一个不变的事件。淀粉样β肽源自一种更大的前体，即普遍表达的淀粉样前体蛋白（APP）。在表达APP形式的不同外周细胞中，血小板特别有趣，因为它们显示出其异构体的浓度与在脑中发现的浓度相当。此外，一些实验室独立描述了与人口统计学特征匹配的对照受试者相比，阿尔茨海默病患者血小板中APP代谢/浓度的改变。这些观察结果确定了我们工作的框架，旨在研究是否能检测到血小板APP形式水平与阿尔茨海默病之间的相关性。我们已经报道，受阿尔茨海默病影响的患者显示出血小板APP形式的差异水平。这一观察结果有几个含义：APP加工异常被认为是阿尔茨海默病在神经元区室中非常早期的变化，确实发生在神经元外组织，如血小板中，因此表明阿尔茨海默病是一种全身性疾病；此外，我们的数据强烈表明，血小板APP形式的差异水平可被视为阿尔茨海默病的潜在外周标志物，能够以良好的敏感性和特异性区分阿尔茨海默病和其他类型的痴呆。
