Disease-related microglia heterogeneity in the hippocampus of Alzheimer's disease, dementia with Lewy bodies, and hippocampal sclerosis of aging.
Disease-related microglia heterogeneity in the hippocampus of Alzheimer's disease, dementia with Lewy bodies, and hippocampal sclerosis of aging.
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DOI：
10.1186/s40478-015-0209-z
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发表时间：
2015-05-23
影响因子：
7.1
通讯作者：
Nelson PT
中科院分区：
文献类型：
--
作者：
Bachstetter AD;Van Eldik LJ;Schmitt FA;Neltner JH;Ighodaro ET;Webster SJ;Patel E;Abner EL;Kryscio RJ;Nelson PT
神经病理学、遗传学和生物化学研究支持小胶质细胞参与阿尔茨海默病(AD)发病机制的假说。尽管阿尔茨海默病的小胶质细胞具有广泛的特征，但仍有许多悬而未决的问题，对其他常见形式的老年性痴呆的小胶质细胞形态也知之甚少，特别是路易体痴呆(DLB)和老年性海马硬化症(HS-Aging)。此外，以前没有研究试图比较和对比不同神经退行性疾病的海马区小胶质细胞的形态。在这里，我们研究了来自肯塔基大学阿尔茨海默病中心尸检队列的经病理证实的AD(n = 7)、HS老化(n = 7)、AD + HS老化(n = 4)、DLB(n = 12)和正常(认知正常)对照组(NC)(n = 9)的病例。我们在尸检标本中定义了五种小胶质细胞的形态表型：分枝状、肥大型、营养不良型、杆状和阿米巴样型。Aperio ScanScope数字神经病理工具与两个著名的小胶质细胞标记物一起使用：IBA1(静止和激活的小胶质细胞标记物)和CD68(巨噬细胞/小胶质细胞中与吞噬细胞相关的溶酶体标记物)。海马体染色分析包括对海马体结构和附近白质的亚区的研究。使用这些工具和方法，我们描述了小胶质细胞特征的变化，这些变化显示出一定程度的疾病特异性，包括：(1)在HS-老化和AD- + HS-老化中小胶质细胞密度和数量增加；(2)小胶质细胞密度降低；(3)在HS-老化中营养不良的小胶质细胞数量增加；(4)营养不良的小胶质细胞占全部小胶质细胞的比例增加。我们得出结论，小胶质细胞和巨噬细胞系细胞之间的形态差异有助于指导未来将神经炎性机制与特定的神经退行性疾病亚型联系起来的工作。
Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer’s disease (AD) pathogenesis. Despite the extensive characterization of AD microglia, there are still many unanswered questions, and little is known about microglial morphology in other common forms of age-related dementia: particularly, dementia with Lewy bodies (DLB) and hippocampal sclerosis of aging (HS-Aging). In addition, no prior studies have attempted to compare and contrast the microglia morphology in the hippocampus of various neurodegenerative conditions. Here we studied cases with pathologically-confirmed AD (n = 7), HS-Aging (n = 7), AD + HS-aging (n = 4), DLB (n = 12), and normal (cognitively intact) controls (NC) (n = 9) from the University of Kentucky Alzheimer’s Disease Center autopsy cohort. We defined five microglia morphological phenotypes in the autopsy samples: ramified, hypertrophic, dystrophic, rod-shaped, and amoeboid. The Aperio ScanScope digital neuropathological tool was used along with two well-known microglial markers: IBA1 (a marker for both resting and activated microglia) and CD68 (a lysosomal marker in macrophages/microglia associated with phagocytic cells). Hippocampal staining analyses included studies of subregions within the hippocampal formation and nearby white matter. Using these tools and methods, we describe variation in microglial characteristics that show some degree of disease specificity, including, (1) increased microglia density and number in HS-aging and AD + HS-aging; (2) low microglia density in DLB; (3) increased number of dystrophic microglia in HS-aging; and (4) increased proportion of dystrophic to all microglia in DLB. We conclude that variations in morphologies among microglial cells, and cells of macrophage lineage, can help guide future work connecting neuroinflammatory mechanisms with specific neurodegenerative disease subtypes.
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影响因子：
5.8
作者：
Mosher, Kira Irving;Wyss-Coray, Tony
通讯作者：
Wyss-Coray, Tony
DOI：
10.1523/jneurosci.5399-12.2013
发表时间：
2013-04-03
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bachstetter AD;Rowe RK;Kaneko M;Goulding D;Lifshitz J;Van Eldik LJ
通讯作者：
Van Eldik LJ
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：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
14.5
作者：
Nelson, Peter T.;Schmitt, Frederick A.;Kryscio, Richard J.
通讯作者：
Kryscio, Richard J.