Leuba Geneviève, Vernay André, Zimmermann Vincent, Saini Krishan, Kraftsik Rudolf, Savioz Armand
Department of Psychiatry, CHUV, Center for Psychiatric Neuroscience, Lausanne, Switzerland.
Brain Res Bull. 2009 Oct 28;80(4-5):196-202. doi: 10.1016/j.brainresbull.2009.06.009. Epub 2009 Jun 25.
In order to understand relationships between executive and structural deficits in the frontal cortex of patients within normal aging or Alzheimer's disease, we studied frontal pathological changes in young and old controls compared to cases with sporadic (AD) or familial Alzheimer's disease (FAD). We performed a semi-automatic computer assisted analysis of the distribution of beta-amyloid (Abeta) deposits revealed by Abeta immunostaining as well as of neurofibrillary tangles (NFT) revealed by Gallyas silver staining in Brodman areas 10 (frontal polar), 12 (ventro-infero-median) and 24 (anterior cingular), using tissue samples from 5 FAD, 6 sporadic AD and 10 control brains. We also performed densitometric measurements of glial fibrillary acidic protein, principal compound of intermediate filaments of astrocytes, and of phosphorylated neurofilament H and M epitopes in areas 10 and 24. All regions studied seem almost completely spared in normal old controls, with only the oldest ones exhibiting a weak percentage of beta-amyloid deposit and hardly any NFT. On the contrary, all AD and FAD cases were severely damaged as shown by statistically significant increased percentages of beta-amyloid deposit, as well as by a high number of NFT. FAD cases (all from the same family) had statistically more beta-amyloid and GFAP than sporadic AD cases in both areas 10 and 24 and statistically more NFT only in area 24. The correlation between the percentage of beta-amyloid and the number of NFT was significant only for area 24. Altogether, these data suggest that the frontal cortex can be spared by AD type lesions in normal aging, but is severely damaged in sporadic and still more in familial Alzheimer's disease. The frontal regions appear to be differentially vulnerable, with area 12 having the less amyloid burden, area 24 the less NFT and area 10 having both more amyloid and more NFT. This pattern of damage in frontal regions may represent a strong neuroanatomical support for the deterioration of attention and cognitive capacities as well as for the presence of emotional and behavioral troubles in AD patients.
为了了解正常衰老或阿尔茨海默病患者额叶皮质中执行功能缺陷与结构缺陷之间的关系，我们研究了年轻和老年对照者与散发性（AD）或家族性阿尔茨海默病（FAD）患者的额叶病理变化。我们使用来自5例FAD、6例散发性AD和10例对照者大脑的组织样本，对β-淀粉样蛋白（Aβ）免疫染色显示的Aβ沉积物分布以及Gallyas银染色显示的布罗德曼区10（额极）、12（腹下正中）和24（前扣带回）中的神经原纤维缠结（NFT）进行了半自动计算机辅助分析。我们还对胶质纤维酸性蛋白（星形胶质细胞中间丝的主要成分）以及10区和24区中磷酸化神经丝H和M表位进行了光密度测量。在正常老年对照者中，所有研究区域似乎几乎完全未受影响，只有最年长者显示出少量的β-淀粉样蛋白沉积物，几乎没有NFT。相反，所有AD和FAD病例均严重受损，表现为β-淀粉样蛋白沉积物百分比在统计学上显著增加，以及大量NFT。FAD病例（均来自同一家族）在10区和24区的β-淀粉样蛋白和胶质纤维酸性蛋白在统计学上均多于散发性AD病例，仅在24区的NFT在统计学上更多。β-淀粉样蛋白百分比与NFT数量之间的相关性仅在24区显著。总之，这些数据表明，在正常衰老过程中，额叶皮质可免受AD型病变的影响，但在散发性AD中严重受损，在家族性阿尔茨海默病中受损更严重。额叶区域似乎易损性不同，12区的淀粉样蛋白负担较轻，24区的NFT较少，10区的淀粉样蛋白和NFT均较多。额叶区域的这种损伤模式可能为AD患者注意力和认知能力的下降以及情绪和行为问题的存在提供了强有力的神经解剖学支持。
