AMYLOID BETA-PROTEIN DEPOSITION IN TISSUES OTHER THAN BRAIN IN ALZHEIMERS-DISEASE
AMYLOID BETA-PROTEIN DEPOSITION IN TISSUES OTHER THAN BRAIN IN ALZHEIMERS-DISEASE
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DOI：
10.1038/341226a0
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发表时间：
1989-09-21
期刊：
影响因子：
64.8
通讯作者：
SELKOE, DJ
中科院分区：
文献类型：
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作者：
JOACHIM, CL;MORI, H;SELKOE, DJ
阿尔茨海默病是老年人进行性智力衰退的最常见原因。定义该疾病的丝状脑损伤发生在神经元内（神经原纤维缠结）、细胞外脑沉积物（淀粉样斑块）和脑膜脑血管内（淀粉样血管病）1,2。几乎所有老年人的大脑中都发现它们的数量较少1。一种相对分子质量 (Mr) 约为 4,000 的蛋白质，称为淀粉样β-蛋白或淀粉样 A4 蛋白，是阿尔茨海默病 3-5、正常衰老 6 和 21 三体症（唐氏综合症）7 个体中血管和斑块淀粉样蛋白丝的亚基。 β 淀粉样蛋白是膜相关糖蛋白 8-13 的一个小片段，由人类 21 号染色体上的一个基因编码，该基因是导致至少某些家族性阿尔茨海默病的遗传缺陷的端粒14,15。到目前为止，尽管非神经组织表型异常的报道16-20表明阿尔茨海默病可能是一种广泛的全身性疾病，但该疾病的病理病变仅在大脑中发现。在此，我们报告了阿尔茨海默病患者的非神经组织和血管（包括皮肤、皮下组织和肠道）中β-淀粉样蛋白沉积物的检测。该蛋白质也存在于部分老年正常受试者的非神经组织中。我们的研究结果表明，疾病过程的一个主要特征在大脑以外的组织中亚临床表达。 β-淀粉样蛋白沉积在多个组织中的出现表明该蛋白可能在许多器官中局部产生，或者可能像其他人类淀粉样变性一样源自共同的循环前体。这些观察结果影响了许多分析阿尔茨海默病脑组织中淀粉样蛋白前体及其信使 RNA 的实验的基本原理，并且对该疾病的发病机制和治疗具有重大意义。
ALZHEIMER'S disease is the most common cause of progressive intellectual failure in aged humans. The filamentous brain lesions which define the disease occur within neurons (neurofibrillary tangles), in extracellular cerebral deposits (amyloid plaques) and in meningocerebral blood vessels (amyloid angiopathy)1,2. They are found in lesser numbers in the brains of virtually all old humans1. A protein with a relative molecular mass (Mr) of ∼4,000, designated amyloidβ-protein or amyloid A4 protein, is the subunit of the vascular and plaque amyloid filaments in individuals with Alzheimer's disease3–5, normal ageing6and trisomy 21 (Down's syndrome)7. The amyloidβ-protein is a small fragment of a membrane-associated glycoprotein8–13, encoded by a gene on human chromosome 21 which is telomeric to a genetic defect that causes at least some cases of familial Alzheimer's disease14,15. Until now, the pathological lesions of the disease have been found only in the brain, although reports of phenotypic abnormalities in non-neural tissues16–20have suggested that Alzheimer's disease may be a widespread, systemic disorder. Here we report the detection of amyloidβ-protein deposits in non-neural tissues and blood vessels of Alzheimer's disease patients, including skin, subcutaneous tissue and intestine. The protein was also present in non-neural tissues in a proportion of aged, normal subjects. Our findings indicate that a principal feature of the disease process is expressed subclinically in tissues other than brain. The occurrence of amyloidβ- protein deposits in multiple tissues suggests that the protein may be produced locally in numerous organs or may, as in other human amyloidoses, be derived from a common circulating precursor. These observations affect the rationale for many experiments analysing the amyloidβ-protein precursor and its messenger RNAs in Alzheimer's disease brain tissue and have major implications for the pathogenesis and treatment of the disease.