Pappolla M A, Omar R A, Sambamurti K, Anderson J P, Robakis N K
Department of Pathology, Mount Sinai School of Medicine, New York, New York 10029-6574.
Am J Pathol. 1992 Nov;141(5):1151-9.
Senile plaques are among the most conspicuous neuropathologic changes found in the brains of elderly individuals and patients with Alzheimer's disease (AD). The origin of the amyloid beta protein (A beta P) that accumulates in senile plaques continues to be highly controversial. Recently, using quantitative immunohistochemistry and computerized image analysis, we obtained evidence that at least a subset of early ("diffuse") senile plaques originate from neurons. In the current investigation, we employed monoclonal antibodies to A beta P and the same computerized methodology to examine in further detail the quantitative patterns of A beta P deposition in diffuse plaques in a population of intellectually intact elderly individuals. The presence of neurocentric concentration gradients of A beta P accumulation was confirmed in this study. Most significantly, this was the most predominant pattern of early amyloid deposition in the population studied. The highest concentration of A beta P was centered around neuronal cell bodies or their processes, and occasionally along neuronal plasma membranes. Computerized images showed patterns that can be interpreted as a pathogenetic sequence ranging from initial neurogenic concentration gradients centered around one single neuron to larger deposits (diffuse plaques) composed of several "anastomosing" gradients involving several adjacent neurons. It is proposed that the described very early deposits constitute the initial stage in the development of the senile plaque. Although this study does not fully prove that the accumulated A beta P is synthesized in the neuron or neuronal process it surrounds, the images herein presented suggest that neurons are the initial nidus of plaque formation.
老年斑是在老年人和阿尔茨海默病（AD）患者大脑中发现的最显著的神经病理学变化之一。在老年斑中积累的β淀粉样蛋白（AβP）的起源一直存在很大争议。最近，我们使用定量免疫组织化学和计算机图像分析，获得了证据表明至少一部分早期（“弥漫性”）老年斑起源于神经元。在当前的研究中，我们使用针对AβP的单克隆抗体和相同的计算机方法，进一步详细检查了一群智力正常的老年人中弥漫性斑块中AβP沉积的定量模式。本研究证实了AβP积累的以神经为中心的浓度梯度的存在。最重要的是，这是所研究人群中早期淀粉样蛋白沉积的最主要模式。AβP的最高浓度集中在神经元细胞体或其突起周围，偶尔也沿着神经元质膜。计算机图像显示的模式可以解释为一种发病机制序列，从围绕单个神经元的初始神经源性浓度梯度到由涉及几个相邻神经元的几个“吻合”梯度组成的更大沉积物（弥漫性斑块）。有人提出，所描述的非常早期的沉积物构成了老年斑发展的初始阶段。虽然这项研究没有完全证明积累的AβP是在它所围绕的神经元或神经突起中合成的，但本文呈现的图像表明神经元是斑块形成的初始病灶。
