Trembath Dimitri, Ervin John F, Broom Lucy, Szymanski Mari, Welsh-Bohmer Kathleen, Pieper Carl, Hulette Christine M
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Acta Neuropathol. 2007 Jan;113(1):23-31. doi: 10.1007/s00401-006-0162-9. Epub 2006 Nov 7.
We performed a comparative study to assess cerebral amyloid angiopathy and ApoE genotype in cases of Alzheimer's disease (AD). Ten ApoE 3,3 and ten ApoE 4,4 AD brains, as well as ten normal control brains, were selected after matching for age, sex, and duration of disease. Sections of middle frontal and inferior parietal cortex including white matter sections were stained with an antibody against amyloid beta (Abeta), and extensive analysis of arteriolar Abeta deposition was performed using digital image analysis. Quantification of the staining revealed a larger cross-section of arteriolar walls occupied by Abeta in ApoE 4,4 and ApoE 3,3 AD subjects compared to controls. Our results show Abeta deposition in gray matter and white matter arterioles was predominantly found in ApoE 4,4 brains and, overall, Abeta deposition was greatest in these cases. This observation implies that there is greater vascular amyloid deposition (particularly in the white matter arterioles) in ApoE 4,4 AD individuals compared to ApoE 3,3 AD. These observations may give insight into the etiology behind the increased risk for AD associated with the ApoE-epsilon4 allele and the pathogenesis of vascular Abeta deposition.
我们进行了一项比较研究,以评估阿尔茨海默病(AD)患者的脑淀粉样血管病和载脂蛋白E(ApoE)基因型。在对年龄、性别和病程进行匹配后,选取了10例ApoE 3,3和10例ApoE 4,4的AD患者大脑,以及10例正常对照大脑。包括白质切片在内的额中回和顶下叶皮质切片用抗淀粉样β蛋白(Aβ)抗体染色,并使用数字图像分析对小动脉Aβ沉积进行广泛分析。染色定量显示,与对照组相比,ApoE 4,4和ApoE 3,3的AD患者中,被Aβ占据的小动脉壁横截面更大。我们的结果表明,灰质和白质小动脉中的Aβ沉积主要见于ApoE 4,4大脑,总体而言,这些病例中的Aβ沉积最为严重。这一观察结果表明,与ApoE 3,3的AD患者相比,ApoE 4,4的AD个体中血管淀粉样蛋白沉积更多(尤其是在白质小动脉中)。这些观察结果可能有助于深入了解与ApoE-ε4等位基因相关的AD风险增加背后的病因以及血管Aβ沉积的发病机制。