McKee A C, Kosik K S, Kowall N W
Department of Neuropathology, Massachusetts General Hospital, Boston 02114.
Ann Neurol. 1991 Aug;30(2):156-65. doi: 10.1002/ana.410300206.
Previous studies of Alzheimer's disease (AD) have correlated the severity of dementia with either the number of senile plaques or neurofibrillary tangles. We used antibodies raised against amyloid beta/A4 protein of senile plaque cores and tau protein as well as thioflavine S and the Campbell-Switzer modification of the Hicks silver method to examine the hippocampal formation and five neocortical regions from 22 nondemented elderly control subjects and 34 demented patients with cerebral senile plaques and neurofibrillary tangles, without complicating disease processes. Ten control subjects (46%) had no beta/A4 protein deposition. Twelve control subjects (54%) had widespread beta/A4 protein deposition but no neocortical neuritic pathology. Of the 34 patients with AD-type changes, 27 (79%) had widespread senile plaques and neurofibrillary tangles, while 7 (21%) had neocortical senile plaques with few neurofibrillary tangles. All demented patients had widespread beta/A4 protein deposition and neocortical tau-immunoreactive, Hicks silver-positive dystrophic neurites. The neurites were found both free in the neuropil as well as surrounding senile plaques. Quantitative analysis showed that dystrophic neurites were significantly increased in patients with AD compared with control subjects and the number of dystrophic neurites and neurofibrillary tangles correlated with the clinical severity of dementia. Widespread cerebral beta/A4 protein deposition may be necessary but by itself is insufficient for the development of dementia in AD.
以往关于阿尔茨海默病（AD）的研究已将痴呆的严重程度与老年斑或神经原纤维缠结的数量联系起来。我们使用针对老年斑核心的淀粉样β/A4蛋白和tau蛋白产生的抗体，以及硫黄素S和希克斯银法的坎贝尔 - 斯威策改良法，对22名无痴呆的老年对照受试者以及34名患有脑老年斑和神经原纤维缠结且无复杂疾病过程的痴呆患者的海马结构和五个新皮质区域进行了检查。10名对照受试者（46%）没有β/A4蛋白沉积。12名对照受试者（54%）有广泛的β/A4蛋白沉积，但没有新皮质神经炎性病变。在34例具有AD型改变的患者中，27例（79%）有广泛的老年斑和神经原纤维缠结，而7例（21%）有新皮质老年斑但神经原纤维缠结较少。所有痴呆患者都有广泛的β/A4蛋白沉积以及新皮质tau免疫反应阳性、希克斯银染色阳性的营养不良性神经突。这些神经突既游离于神经毡中，也存在于老年斑周围。定量分析表明，与对照受试者相比，AD患者的营养不良性神经突显著增加，且营养不良性神经突和神经原纤维缠结的数量与痴呆的临床严重程度相关。广泛的脑β/A4蛋白沉积可能是必要的，但仅凭其自身不足以导致AD患者发生痴呆。
