Olfactory epithelium amyloid-beta and paired helical filament-tau pathology in Alzheimer disease.
Olfactory epithelium amyloid-beta and paired helical filament-tau pathology in Alzheimer disease.
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DOI：
10.1002/ana.21910
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发表时间：
2010-04
影响因子：
11.2
通讯作者：
Trojanowski, John Q.
中科院分区：
文献类型：
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作者：
Arnold, Steven E.;Lee, Edward B.;Moberg, Paul J.;Stutzbach, Lauren;Kazi, Hala;HanMs, Li-Ying;Lee, Virginia M. Y.;Trojanowski, John Q.
嗅觉功能障碍在阿尔茨海默病（AD）和其他神经退行性疾病中很常见。PHFtau、α-突触核蛋白和淀粉样蛋白-β病变在嗅觉系统的大脑区域中发生早期和严重，并且它们也在嗅觉上皮（OE）中观察到。然而，他们的频率，丰度，疾病特异性，以及OE病理学脑病理学的关系尚未建立。我们研究了79例AD患者、63例各种其他神经退行性疾病患者和45例神经病理正常患者的尸检OE中淀粉样蛋白-β、PHFtau、α-突触核蛋白和TDP-43的病理表达。71%的AD病例中β淀粉样蛋白呈点状和小片状聚集体，而正常病例为22%，其他疾病病例为14%，AD中β淀粉样蛋白的含量高于其他两种诊断类别。PHFtau在55%的AD病例、34%的正常脑病例和39%的其他神经退行性疾病病例中的营养不良神经突中明显，在AD中也具有较高的密度。在7例患者中，α-突触核蛋白存在于营养不良的神经突中，其中6例还具有脑路易体。在任何情况下，在OE中均未观察到病理性TDP-43夹杂物。OE中的淀粉样蛋白-β和较小程度的PHFtau评级与大脑中的皮质Aβ和PHFtau病变评级显著相关。这些数据表明，在OE中的AD病理学存在于大多数病理学证实的AD病例中，并与脑病理学相关。未来的工作可能会评估淀粉样蛋白-β和PHFtau测量在OE中作为AD生物标志物的效用。
Olfactory dysfunction is common in Alzheimer’s disease (AD) and other neurodegenerative diseases. PHFtau, α-synuclein and amyloid-β lesions occur early and severely in cerebral regions of the olfactory system and they have also been observed in olfactory epithelium (OE). However, their frequency, abundance, disease specificity, and relationships of OE pathology to brain pathology have not been established. We investigated the pathological expression of amyloid-β, PHFtau, α-synuclein, and TDP-43 in postmortem OE of 79 cases with AD, 63 cases with various other neurodegenerative diseases, and 45 neuropathologically normal cases. Amyloid-β was present as punctate and small patchy aggregates in 71% of AD cases compared to 22% of normal cases and 14% of cases with other diseases and in greater amounts in AD than either of the other two diagnostic categories. PHFtau was evident in dystrophic neurites in 55% of cases with AD, 34% with normal brains, and 39% with other neurodegenerative diseases, also at higher densities in AD. α-Synuclein was present in dystrophic neurites in seven cases, six of whom also had cerebral Lewy bodies. Pathological TDP-43 inclusions were not observed in the OE in any cases. Amyloid-β and to a lesser degree, PHFtau ratings in OE significantly correlated with cortical Aβ and PHFtau lesion ratings in the brain. These data demonstrate that AD pathology in the OE is present in the majority of cases with pathologically verified AD and correlates with brain pathology. Future work may assess the utility of amyloid-β and PHFtau measurement in OE as a biomarker for AD.
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影响因子：
3.7
作者：
Arnold, Steven E.;Hyman, Bradley T.;Van Hoesen, Gary W.
通讯作者：
Van Hoesen, Gary W.
影响因子：
--
作者：
Geser, Felix;Brandmeir, Nicholas J.;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
1.4
作者：
CRINO, PB;MARTIN, JA;TROJANOWSKI, JQ
通讯作者：
TROJANOWSKI, JQ
影响因子：
2.4
作者：
Hock, C;Golombowski, S;Unger, J
通讯作者：
Unger, J
影响因子：
5.3
作者：
Duda, JE;Shah, U;Trojanowski, JQ
通讯作者：
Trojanowski, JQ