Neocortical Variation of Aβ Load in Fully Expressed, Pure Alzheimer's Disease
Neocortical Variation of Aβ Load in Fully Expressed, Pure Alzheimer's Disease
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DOI：
10.3233/jad-2010-1205
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Giaccone, Giorgio
中科院分区：
文献类型：
--
作者：
Cupidi, Chiara;Capobianco, Raffaella;Giaccone, Giorgio
淀粉样β蛋白（A β）沉积与tau蛋白相关神经病理改变之间的关系是阿尔茨海默病（AD）发病机制中的关键问题。本研究的目的是调查39例完全表达AD患者A β和tau病理的程度和皮质分布，它们之间的相互联系及其与疾病持续时间的相关性。通过tau蛋白免疫组化，我们确定了Braak V期和VI期神经病理学变化的不同分布模式。在Braak阶段VI的患者中，疾病的持续时间比在V.在几个新皮层区域进行的形态测量分析更长，表明A β负荷在个体之间是不均匀的，并且在同一患者的整个新皮层中也是不同的，显示出运动前区和初级运动区的关联领域的严重程度降低。在Braak VI期，β负荷高于V期，并且与初级运动皮层和上级颞回的病程呈正相关。总体而言，我们记录到即使在疾病的最后阶段，AD大脑中A β沉积的程度也存在显着的异质性，这无法完全用疾病过程中大脑皮质中这种病理蛋白的简单、定期积累来解释。这项研究可能与正确评价AD的治疗策略有关，这些治疗策略专门针对A β病理学。
The relationship between amyloid-beta (A beta) deposition and tau-related neurofibrillary changes is a key issue in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to investigate the extent and cortical distribution of A beta and tau pathology, their mutual links and their correlation with the duration of the disease in thirty-nine patients with fully expressed AD. By tau immunohistochemistry, we identified different patterns of distribution of neurofibrillary changes that were ascribed to Braak stage V and VI. The disease duration was longer in patients at Braak stage VI than in those at V. Morphometric analysis carried out in several neocortical areas demonstrated that A beta load was not uniform among individuals and also varied in the same patient throughout the neocortex, showing decreased severity from associative fields in the premotor and primary motor areas. A beta load was higher at Braak stage VI than at stage V and correlated positively with disease duration in primary motor cortex and in superior temporal gyrus. Overall, we documented a marked heterogeneity in the extent of A beta deposition even in AD brains at final stages of disease that cannot be completely explained by a simple, regular build up of this pathologic protein in the cerebral cortex during the course of the disease. This study may be relevant for the correct evaluation of therapeutic strategies for AD that specifically address A beta pathology.