Cummings B J, Cotman C W
Institute for Brain Aging and Dementia, University of California, Irvine 92717-4550, USA.
Lancet. 1995 Dec 9;346(8989):1524-8. doi: 10.1016/s0140-6736(95)92053-6.
The protein beta-amyloid is said to be central to the disease process of Alzheimer's disease (AD). Several groups have developed transgenic models that overexpress the amyloid precursor protein or beta-amyloid and then develop AD-like neuropathology. Another report suggests that beta-amyloid accumulation in old dogs correlates with cognitive impairment. However, many other researchers argue that beta-amyloid deposition in senile plaques is a secondary event because plaque numbers in man do not correlate well with cognition. We set out to analyse this conumdrum in man. We selected 16 mild to severely demented AD cases on the basis of mini-mental state exam scores (MMSE; n = 16). We also included 4 controls who represented the upper range of cognitive ability. We used a computer-based image analysis of cross-sectional area of the brain occupied by beta-amyloid immunopositive deposition. We used this technique in preference to conventional methods of manual plaque counts and found a strong relation between beta-amyloid load in entorhinal cortex and cognition measured on various scales (r = -0.93 versus the Blessed IMC). Our study suggests that the size of cortical area affected by beta-amyloid deposition is an important factor in the clinical manifestation of dementia, and lends support to the possibility that beta-amyloid is central to the aetiology of AD.
蛋白质β-淀粉样蛋白被认为是阿尔茨海默病（AD）疾病进程的核心。有几个研究小组开发了转基因模型，这些模型过度表达淀粉样前体蛋白或β-淀粉样蛋白，随后出现类似AD的神经病理学变化。另一项报告表明，老年犬体内β-淀粉样蛋白的积累与认知障碍有关。然而，许多其他研究人员认为，老年斑中的β-淀粉样蛋白沉积是一个继发事件，因为在人类中斑块数量与认知能力并没有很好的相关性。我们着手在人类中分析这一难题。我们根据简易精神状态检查表（MMSE）评分选择了16例轻度至重度痴呆的AD病例（n = 16）。我们还纳入了4名代表认知能力上限的对照者。我们使用基于计算机的图像分析来测量β-淀粉样蛋白免疫阳性沉积所占据的脑横截面积。我们优先使用这种技术而非传统的手动计数斑块的方法，并且发现内嗅皮质中的β-淀粉样蛋白负荷与通过各种量表测量的认知能力之间存在很强的相关性（与Blessed IMC相比，r = -0.93）。我们的研究表明，受β-淀粉样蛋白沉积影响的皮质区域大小是痴呆临床表现的一个重要因素，并支持β-淀粉样蛋白是AD病因核心的可能性。
