Focal demyelination in Alzheimer's disease and transgenic mouse models
Focal demyelination in Alzheimer's disease and transgenic mouse models
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DOI：
10.1007/s00401-010-0657-2
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发表时间：
2010-05-01
影响因子：
12.7
通讯作者：
Dickson, Tracey C.
中科院分区：
文献类型：
--
作者：
Mitew, Stanislaw;Kirkcaldie, Matthew T. K.;Dickson, Tracey C.
我们研究了在人类组织和相关的转基因小鼠模型中与A β斑块相关的髓鞘的改变，A β斑块是阿尔茨海默病（AD）的主要病理标志。使用定量形态学技术，我们确定，与年龄匹配的对照组织相比，在人类早老素-1家族性、散发性和临床前AD病例以及两种AD小鼠转基因模型中，新皮质灰质中的纤维状A β病理与局灶性脱髓鞘相关。这种脱髓鞘在A β斑块的核心最为明显。此外，我们发现，在散发性和临床前AD病例中，与A β斑块核心相关的少突胶质细胞局灶性丢失。在人类和转基因小鼠中，与对照组相比，无斑块的新皮层区域没有明显的脱髓鞘或少突胶质细胞损失。与斑块相关的营养不良神经突也脱髓鞘。我们认为，这种斑块相关的皮质灰质局灶性脱髓鞘可能会损害皮质加工，也可能与异常轴突发芽，营养不良性神经突形成的基础。
We have investigated alterations in myelin associated with A beta plaques, a major pathological hallmark of Alzheimer's disease (AD), in human tissue and relevant transgenic mice models. Using quantitative morphological techniques, we determined that fibrillar A beta pathology in the grey matter of the neocortex was associated with focal demyelination in human presenilin-1 familial, sporadic and preclinical AD cases, as well as in two mouse transgenic models of AD, compared with age-matched control tissue. This demyelination was most pronounced at the core of A beta plaques. Furthermore, we found a focal loss of oligodendrocytes in sporadic and preclinical AD cases associated with A beta plaque cores. In human and transgenic mice alike, plaque-free neocortical regions showed no significant demyelination or oligodendrocyte loss compared with controls. Dystrophic neurites associated with the plaques were also demyelinated. We suggest that such plaque-associated focal demyelination of the cortical grey matter might impair cortical processing, and may also be associated with aberrant axonal sprouting that underlies dystrophic neurite formation.