Neuroinflammation is increased in the parietal cortex of atypical Alzheimer's disease.
Neuroinflammation is increased in the parietal cortex of atypical Alzheimer's disease.
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DOI：
10.1186/s12974-018-1180-y
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发表时间：
2018-05-29
影响因子：
9.3
通讯作者：
Bouwman FH
中科院分区：
文献类型：
--
作者：
Boon BDC;Hoozemans JJM;Lopuhaä B;Eigenhuis KN;Scheltens P;Kamphorst W;Rozemuller AJM;Bouwman FH
虽然大多数阿尔茨海默病 (AD) 患者会出现记忆障碍，但 30% 的早期发病患者会出现非遗忘症状。这种非典型表现被认为是由神经原纤维缠结（NFT）的不同扩散引起的，与 Braak 和 Braak 最初提出的不同。最近的研究表明神经炎症在 tau 病理学的传播中发挥着重要作用。我们的目的是探讨 AD 病理学的非典型传播是否与神经炎症的非典型分布有关。根据 NFT 分布和遗忘或非遗忘临床表现选择典型和非典型 AD 病例。对10例典型和9例非典型AD病例的颞极和顶叶上叶进行免疫组织化学检测。通过图像分析对β淀粉样蛋白（N端；IC16）、pTau（AT8）、反应性星形胶质细胞（GFAP）、小胶质细胞（Iba1、CD68和HLA-DP/DQ/DR）和补体因子（C1q、C3d、C4b和C5b-9）的存在进行定量。使用线性混合模型对免疫反应性的叶分布模式的差异进行统计评估。我们发现淀粉样蛋白-β、GFAP 和 Iba1 在典型和非典型 AD 中均呈时间主导分布。 AD 变体之间 pTau、CD68、HLA-DP/DQ/DR、C3d 和 C4b 的分布不同。典型的 AD 病例显示这些标记物的时间显性分布，而非典型的 AD 病例显示顶叶显性分布。有趣的是，当量化β淀粉样斑块的数量而不是染色表面积时，非典型AD病例的分布模式与典型AD病例不同。值得注意的是，两种表型之间的斑块形态和斑块内神经炎症的定位是不同的。我们的数据显示 AD 表型之间神经炎症标志物和淀粉样蛋白斑块的不同定位。此外，这些标记物反映了非典型 AD 中 tau 病理学的非典型分布，表明神经炎症可能是 β 淀粉样蛋白沉积、tau 病理学和临床症状之间的重要联系。
While most patients with Alzheimer’s disease (AD) present with memory complaints, 30% of patients with early disease onset present with non-amnestic symptoms. This atypical presentation is thought to be caused by a different spreading of neurofibrillary tangles (NFT) than originally proposed by Braak and Braak. Recent studies suggest a prominent role for neuroinflammation in the spreading of tau pathology. We aimed to explore whether an atypical spreading of pathology in AD is associated with an atypical distribution of neuroinflammation. Typical and atypical AD cases were selected based on both NFT distribution and amnestic or non-amnestic clinical presentation. Immunohistochemistry was performed on the temporal pole and superior parietal lobe of 10 typical and 9 atypical AD cases. The presence of amyloid-beta (N-terminal; IC16), pTau (AT8), reactive astrocytes (GFAP), microglia (Iba1, CD68, and HLA-DP/DQ/DR), and complement factors (C1q, C3d, C4b, and C5b-9) was quantified by image analysis. Differences in lobar distribution patterns of immunoreactivity were statistically assessed using a linear mixed model. We found a temporal dominant distribution for amyloid-beta, GFAP, and Iba1 in both typical and atypical AD. Distribution of pTau, CD68, HLA-DP/DQ/DR, C3d, and C4b differed between AD variants. Typical AD cases showed a temporal dominant distribution of these markers, whereas atypical AD cases showed a parietal dominant distribution. Interestingly, when quantifying for the number of amyloid-beta plaques instead of stained surface area, atypical AD cases differed in distribution pattern from typical AD cases. Remarkably, plaque morphology and localization of neuroinflammation within the plaques was different between the two phenotypes. Our data show a different localization of neuroinflammatory markers and amyloid-beta plaques between AD phenotypes. In addition, these markers reflect the atypical distribution of tau pathology in atypical AD, suggesting that neuroinflammation might be a crucial link between amyloid-beta deposits, tau pathology, and clinical symptoms.
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影响因子：
16.2
作者：
Bhaskar, Kiran;Konerth, Megan;Kokiko-Cochran, Olga N.;Cardona, Astrid;Ransohoff, Richard M.;Lamb, Bruce T.
通讯作者：
Lamb, Bruce T.
影响因子：
25
作者：
Asai H;Ikezu S;Tsunoda S;Medalla M;Luebke J;Haydar T;Wolozin B;Butovsky O;Kügler S;Ikezu T
通讯作者：
Ikezu T
影响因子：
4.6
作者：
Luo W;Liu W;Hu X;Hanna M;Caravaca A;Paul SM
通讯作者：
Paul SM
影响因子：
2.5
作者：
MCGEER, PL;AKIYAMA, H;MCGEER, EG
通讯作者：
MCGEER, EG
影响因子：
14.5
作者：
Maphis, Nicole;Xu, Guixiang;Bhaskar, Kiran
通讯作者：
Bhaskar, Kiran