Highet Blake, Dieriks Birger Victor, Murray Helen C, Faull Richard L M, Curtis Maurice A
Department of Anatomy and Medical Imaging, Faculty of Medical and Health Science, The University of Auckland, Auckland, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Science, The University of Auckland, Auckland, New Zealand.
Front Aging Neurosci. 2020 Aug 18;12:261. doi: 10.3389/fnagi.2020.00261. eCollection 2020.
Olfactory deficits are an early and prevalent non-motor symptom of Huntington's disease (HD). In other neurodegenerative diseases where olfactory deficits occur, such as Alzheimer's disease and Parkinson's disease, pathological protein aggregates (tau, β-amyloid, α-synuclein) accumulate in the anterior olfactory nucleus (AON) of the olfactory bulb (OFB). Therefore, in this study we determined whether aggregates are also present in HD OFBs; 13 HD and five normal human OFBs were stained for mutant huntingtin (mHtt), tau, β-amyloid, TDP-43, and α-synuclein. Our results show that mHtt aggregates detected with 1F8 antibody are present within all HD OFBs, and mHtt aggregate load in the OFB does not correlate with Vonsattel grading scores. The majority of the aggregates were located in the AON and in similar abundance in each anatomical segment of the AON. No mHtt aggregates were found in controls; 31% of HD cases also contained tau neurofibrillary tangles within the AON. This work demonstrates HD pathology in the OFB and indicates that disease-specific protein aggregation in the AON is a common feature of neurodegenerative diseases that show olfactory deficits.
嗅觉减退是亨廷顿舞蹈症(HD)早期且常见的非运动症状。在其他出现嗅觉减退的神经退行性疾病中,如阿尔茨海默病和帕金森病,病理蛋白聚集体(tau蛋白、β-淀粉样蛋白、α-突触核蛋白)在嗅球(OFB)的前嗅核(AON)中积累。因此,在本研究中,我们确定HD患者的嗅球中是否也存在聚集体;对13例HD患者和5例正常人的嗅球进行突变型亨廷顿蛋白(mHtt)、tau蛋白、β-淀粉样蛋白、TDP-43和α-突触核蛋白染色。我们的结果显示,用1F8抗体检测到的mHtt聚集体存在于所有HD患者的嗅球中,且嗅球中mHtt聚集体负荷与冯·萨特尔分级评分无关。大多数聚集体位于前嗅核,且在前嗅核的每个解剖节段中丰度相似。在对照组中未发现mHtt聚集体;31%的HD病例在前嗅核中也含有tau神经原纤维缠结。这项研究证明了嗅球中的HD病理学特征,并表明前嗅核中疾病特异性蛋白聚集是出现嗅觉减退的神经退行性疾病的共同特征。