Association of CD33 polymorphism rs3865444 with Alzheimer's disease pathology and CD33 expression in human cerebral cortex.
Association of CD33 polymorphism rs3865444 with Alzheimer's disease pathology and CD33 expression in human cerebral cortex.
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DOI：
10.1016/j.neurobiolaging.2014.09.023
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发表时间：
2015-02
影响因子：
4.2
通讯作者：
Lue LF
中科院分区：
文献类型：
--
作者：
Walker DG;Whetzel AM;Serrano G;Sue LI;Beach TG;Lue LF
最近的研究发现，CD 33基因单核苷酸多态性rs3865444中存在的次要A等位基因与阿尔茨海默病（AD）的发病风险降低相关。CD 33（Siglec-3）是一种免疫功能蛋白，具有抗炎信号传导、细胞粘附和内吞功能，其与唾液酸修饰的蛋白质或脂质作为配体。本研究旨在探讨rs3865444基因多态性是否影响AD的发生发展以及CD 33 mRNA和蛋白的表达。在这项研究中，我们利用96个非痴呆症（ND）和97 AD神经病理诊断病例的DNA，以确定不同的rs3865444等位基因，并与AD病理学的不同措施。使用斑块和缠结病理学的半定量组织学测量，我们发现这些疾病组中不同基因型之间没有显著差异。然而，在颞叶皮质脑样品中，CD 33 mRNA表达的增加与AD病理学的增加相关。我们还发现，与A/A等位基因的情况下，颞叶皮质的CD 33蛋白水平降低，但增加了小胶质细胞蛋白IBA-1的水平。使用免疫组织化学颞叶皮质部分，CD 33被选择性地定位于小胶质细胞，在激活的小胶质细胞中表达更大。引起脑内小胶质细胞CD 33表达增加的因素尚不清楚，尽管遗传和疾病因素都参与其中。用淀粉样β（Aβ）肽和一系列其他炎症激活剂处理从尸检脑中分离的人小胶质细胞，导致CD 33 mRNA和蛋白水平降低。
Recent findings identified the minor A allele present in the single nucleotide polymorphism rs3865444 in the CD33 gene as being associated with reduced risk of developing Alzheimer’s disease (AD). CD33 (Siglec-3) is an immune function protein with anti-inflammatory signaling, cell adhesion and endocytosis functions with sialic acid-modified proteins or lipids as ligands. Its involvement in AD pathological mechanisms is still unclear, so the goal of this study was to investigate if the rs3865444 polymorphism affects development of AD pathology and the expression of CD33 mRNA and protein. For this study, we utilized DNA from 96 non-demented (ND) and 97 AD neuropathologically diagnosed cases to identify the different rs3865444 alleles and correlate with different measures of AD pathology. Using semi-quantitative histological measures of plaque and tangle pathology, we saw no significant differences between the different genotypes within these disease groups. However, increased expression of CD33 mRNA was associated with increasing AD pathology in temporal cortex brain samples. We also showed that cases with A/A alleles had reduced levels of CD33 protein in temporal cortex, but increased levels of the microglia protein IBA-1. Using immunohistochemistry on temporal cortex sections, CD33 was selectively localized to microglia, with greater expression in activated microglia. The factors causing increased CD33 expression by microglia in brain are still unclear, although both genetic and disease factors are involved. Treatment of human microglia isolated from autopsy brains with amyloid beta (Aβ) peptide and a range of other inflammatory activating agents resulted in reduced CD33 mRNA and protein levels.
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影响因子：
15.1
作者：
Chakrabarty P;Herring A;Ceballos-Diaz C;Das P;Golde TE
通讯作者：
Golde TE
DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
影响因子：
5.1
作者：
Jiang, Teng;Yu, Jin-Tai;Tan, Lan
通讯作者：
Tan, Lan
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3
作者：
Gonzalez Y;Herrera MT;Soldevila G;Garcia-Garcia L;Fabián G;Pérez-Armendariz EM;Bobadilla K;Guzmán-Beltrán S;Sada E;Torres M
通讯作者：
Torres M