LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease
LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease
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DOI：
10.1097/01.jnen.0000228205.19915.20
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发表时间：
2006-09-01
影响因子：
3.2
通讯作者：
Lah, James J.
中科院分区：
文献类型：
--
作者：
Dodson, Sara E.;Gearing, Marla;Lah, James J.
LR 11是一种在大脑中富集的ApoE受体。我们已经证明，LR 11在散发性阿尔茨海默病（AD）患者中显著下调。这一发现使我们探索LR 11表达减少是否反映了疾病的主要机制或仅仅是其他AD相关变化的次要后果。因此，在AD和家族性AD（FAD）脑的转基因小鼠模型中评估LR 11表达。PS1/APP转基因和野生型小鼠LR 11的免疫组织化学和免疫印迹表明，LR 11水平不受基因型或淀粉样蛋白病理学积累的影响。LR 11表达也基于免疫印迹和LR 11免疫染色强度在对照、散发性AD和FAD（包括早老素-1（PSI）和早老素-2（PS2）突变的病例）中的人额叶皮质中进行评估。虽然LR 11在散发性AD中减少，但对照组和FAD病例之间的蛋白水平或染色强度没有差异。LR 11表达在AD小鼠模型和常染色体显性形式的AD中均不受影响的发现表明LR 11不受淀粉样蛋白积累或其他AD神经病理学变化的调节。我们推测LR 11缺失可能是散发性AD特有的，并通过独立于FAD突变调控的底物-酶相互作用的机制影响淀粉样蛋白病理学。
LR11 is an ApoE receptor that is enriched in the brain. We have shown that LR11 is markedly downregulated in patients with sporadic Alzheimer disease (AD). This finding led us to explore whether reduced LR11 expression reflects a primary mechanism of disease or merely a secondary consequence of other AD-associated changes. Therefore, LR11 expression was assessed in a transgenic mouse model of AD and familial AD (FAD) brains. Immunohistochernistry and immunoblotting of LR11 in PS1/APP transgenic and wild-type mice indicated that LR11 levels are not affected by genotype or accumulation of amyloid pathology. LR11 expression was also evaluated based on immunoblotting and LR11 immunostaining intensity in human frontal cortex in controls, sporadic AD, and FAD, including cases with presenilin-1 (PSI) and presenilin-2 (PS2) mutations. Although LR11 was reduced in sporadic AD, there was no difference in protein level or staining intensity between control and FAD cases. The finding that LR11 expression is unaffected in both a mouse model of AD and autosomal-dominant forms of AD suggests that LR11 is not regulated by amyloid accumulation or other AD neuropathologic changes. We hypothesize that LR11 loss may be specific to sporadic AD and influence amyloid pathology through mechanisms independent of substrate-enzyme interactions regulated by FAD mutations.