阿尔茨海默病患者嗅上皮的淀粉样β和双螺旋丝-tau 病理学。
Olfactory epithelium amyloid-beta and paired helical filament-tau pathology in Alzheimer disease.
机构信息
Alzheimer's Disease Core Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Ann Neurol. 2010 Apr;67(4):462-9. doi: 10.1002/ana.21910.
OBJECTIVE
Olfactory dysfunction is common in Alzheimer disease (AD) and other neurodegenerative diseases. Paired helical filament (PHF)-tau, alpha-synuclein, and amyloid-beta 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, and disease specificity, and the relationships of OE pathology to brain pathology have not been established.
METHODS
We investigated the pathological expression of amyloid-beta, PHFtau, alpha-synuclein, and TDP-43 in postmortem OE of 79 cases with AD, 63 cases with various other neurodegenerative diseases, and 45 neuropathologically normal cases.
RESULTS
Amyloid-beta was present as punctate and small patchy aggregates in 71% of AD cases, compared with 22% of normal cases and 14% of cases with other diseases, and in greater amounts in AD than in either of the other 2 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. alpha-Synuclein was present in dystrophic neurites in 7 cases, 6 of which also had cerebral Lewy bodies. Pathological TDP-43 inclusions were not observed in the OE in any cases. Amyloid-beta and to a lesser degree, PHFtau ratings in OE significantly correlated with cortical Abeta and PHFtau lesion ratings in the brain.
INTERPRETATION
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-beta and PHFtau measurement in OE as a biomarker for AD.
目的
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。配对螺旋丝（PHF）-tau、α-突触核蛋白和淀粉样β病变在嗅觉系统的大脑区域中早期且严重发生，并且在嗅上皮（OE）中也观察到了这些病变。然而，OE 病理学与大脑病理学之间的关系及其与大脑病理学之间的关系尚未确定。
方法
我们研究了 79 例 AD、63 例其他各种神经退行性疾病和 45 例神经病理学正常病例的尸检 OE 中淀粉样β、PHFtau、α-突触核蛋白和 TDP-43 的病理表达。
结果
在 71%的 AD 病例中，淀粉样β呈点状和小斑块状聚集，而在 22%的正常病例和 14%的其他疾病病例中则为点状和小斑块状聚集，在 AD 中的含量高于其他 2 种诊断类别。在 55%的 AD 病例中，PHFtau 可见于营养不良的轴突中，在 34%的正常脑和 39%的其他神经退行性疾病病例中也可见到，AD 中的密度更高。α-突触核蛋白存在于 7 例营养不良的轴突中，其中 6 例也存在脑路易体。在任何病例中，OE 中均未观察到病理性 TDP-43 包涵体。OE 中的淀粉样β和 PHFtau 评分与大脑中的皮质 Abeta 和 PHFtau 病变评分显著相关。
结论
这些数据表明，OE 中的 AD 病理学在大多数经病理证实的 AD 病例中均存在，并与大脑病理学相关。未来的工作可能会评估在 OE 中测量淀粉样β和 PHFtau 作为 AD 生物标志物的效用。
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