Jeynes Brian, Provias John
Faculty of Applied Health Sciences, Department of Community Health Sciences, Brock University, St. Catherines, ON, Canada, L2S 3A1.
Acta Neuropathol. 2006 Oct;112(4):417-27. doi: 10.1007/s00401-006-0099-z. Epub 2006 Jul 8.
Recent studies have observed beta-amyloid-positive capillaries in lesion-prone regions of Alzheimer's disease (AD) brains. It is possible that there is a pathogenic link between neurofibrillary tangles (NFTs) and/or senile plaques (SPs) and altered capillary structure/function. In this study, we examined and compared brain tissue from a frequently observed NFT abundant area, the superior temporal cortex (ST), and a comparatively much NFT sparser area, the calcarine cortex (COC), in ten AD and ten normal adult control brain samples. We recorded the densities of NFTs, and beta-amyloid(8-17,40,42) peptide forms in SPs, capillaries and large vessels [cerebral amyloid angiopathy (CAA)] in these areas. Our results demonstrated that there was a significant difference between the means of NFT and SP beta(8-17,40) lesions when comparing the ST and COC cortical regions in both AD and control brains. In AD brains, we observed a positive correlation between NFTs and SPs in both regions, and between NFTs and beta-amyloid-positive capillaries and CAA vessels, particularly in the calcarine cortex. In addition, significant correlations were observed between some SP beta-amyloid peptide forms and CAA beta(42), in particular, in both regions. These new observations support the view that there are regional (focal) differences in the presence of each AD lesion, and that there may be a pathogenic relationship between the development of AD lesions and beta-amyloid-positive vessels. The data are also consistent with the concept that a focally dysfunctional blood-brain barrier (BBB) that is unable to regulate the influx/efflux of neurotoxic amyloid peptides may participate in the pathogenesis of AD lesions.
最近的研究在阿尔茨海默病（AD）大脑的易损区域观察到了β-淀粉样蛋白阳性的毛细血管。神经纤维缠结（NFTs）和/或老年斑（SPs）与毛细血管结构/功能改变之间可能存在致病联系。在本研究中，我们检查并比较了10例AD和10例正常成人对照脑样本中一个经常观察到NFT丰富的区域——颞上皮质（ST），以及一个NFT相对稀少得多的区域——距状皮质（COC）的脑组织。我们记录了这些区域中NFTs的密度，以及SPs、毛细血管和大血管[脑淀粉样血管病（CAA）]中β-淀粉样蛋白（8-17、40、42）肽的形式。我们的结果表明，在AD和对照大脑中，比较ST和COC皮质区域时，NFT和SPβ（8-17、40）病变的平均值之间存在显著差异。在AD大脑中，我们观察到两个区域的NFTs与SPs之间，以及NFTs与β-淀粉样蛋白阳性毛细血管和CAA血管之间呈正相关，特别是在距状皮质。此外，在两个区域中，尤其是某些SPβ-淀粉样肽形式与CAAβ（42）之间观察到显著相关性。这些新观察结果支持这样一种观点，即每种AD病变的存在存在区域（局灶性）差异，并且AD病变的发展与β-淀粉样蛋白阳性血管之间可能存在致病关系。这些数据也与这样一种概念一致，即局部功能失调的血脑屏障（BBB）无法调节神经毒性淀粉样肽的流入/流出，可能参与了AD病变的发病机制。
