The impact of different presenilin 1 and presenilin 2 mutations on amyloid deposition, neurofibrillary changes and neuronal loss in the familial Alzheimer's disease brain -: Evidence for other phenotype-modifying factors
The impact of different presenilin 1 and presenilin 2 mutations on amyloid deposition, neurofibrillary changes and neuronal loss in the familial Alzheimer's disease brain -: Evidence for other phenotype-modifying factors
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DOI：
10.1093/brain/122.9.1709
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发表时间：
1999-09-01
期刊：
影响因子：
14.5
通讯作者：
Hyman, BT
中科院分区：
文献类型：
--
作者：
Gómez-Isla, T;Growdon, WB;Hyman, BT
为了评估早老素1（PS1）和2（PS2）突变对淀粉样蛋白沉积、神经元缠结（NFT）形成和神经元丢失的影响，我们对30例携带10种不同PSI和PSZ突变的家族性阿尔茨海默病患者的高级联合皮质（上级颞沟）进行了体视学计数，51例散发性阿尔茨海默病病例和33例非痴呆对照受试者。与散发性阿尔茨海默病患者相比，本系列研究中评估的所有PS1和PS2突变均导致总A β和A β（x-42/43）老年斑在上级颞沟中的沉积增加，但A β（x-40）老年斑没有增加。与散发性阿尔茨海默病患者相比，研究的一些PS1突变（M139 V，I143 F，G209 V，R269 H，E280 A），而不是其他突变，也与NFT形成的更快速率和大多数携带它们的患者的神经元丢失加速有关。此外，我们的分析表明，即使在具有相同PS突变的家庭成员中，临床和神经病理学特征也可能存在显著的数量差异，这表明进一步的个体或谱系遗传或表观遗传因素可能强烈调节PS表型。
To assess the influence of the presenilin 1 (PS1) and 2 (PS2) mutations on amyloid deposition, neurofibrillary tangle (NFT) formation and neuronal loss, we performed stereologically based counts in a high-order association cortex, the superior temporal sulcus, of 30 familial Alzheimer's disease cases carrying 10 different PSI and PSZ mutations, 51 sporadic Alzheimer's disease cases and 33 non-demented control subjects. All the PS1 and PS2 mutations assessed in this series led to enhanced deposition of total A beta and A beta(x-42/43) but not A beta(x-40) senile plaques in the superior temporal sulcus when compared with brains from sporadic Alzheimer's disease patients. Some of the PS1 mutations studied (M139V, I143F, G209V, R269H, E280A), but not others, were also associated with faster rates of NFT formation and accelerated neuronal loss in the majority of the patients who harboured them when compared with sporadic Alzheimer's disease patients. In addition, our analysis showed that dramatic quantitative differences in clinical and neuropathological features can exist even among family members with the identical PS mutation, This suggests that further individual or pedigree genetic or epigenetic factors are likely to modulate PS phenotypes strongly.