Neuropathology of Beta-propeller protein associated neurodegeneration (BPAN): a new tauopathy.
Neuropathology of Beta-propeller protein associated neurodegeneration (BPAN): a new tauopathy.
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DOI：
10.1186/s40478-015-0221-3
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发表时间：
2015-06-30
影响因子：
7.1
通讯作者：
Holton JL
中科院分区：
文献类型：
--
作者：
Paudel R;Li A;Wiethoff S;Bandopadhyay R;Bhatia K;de Silva R;Houlden H;Holton JL
β-螺旋桨蛋白相关神经变性（BPAN）与染色体Xp 11上WD重复结构域45（WDR 45）基因突变相关，导致自噬通量降低。本研究描述了一个51岁女性BPAN病例的临床和神经病理学特征。临床病史包括童年以来的学习障碍和进行性步态异常，随后在成年早期出现进行性肌张力障碍特征。脑部影像学检查显示全身性脑萎缩，苍白球和黑质双侧矿化。主要病理改变为黑质铁沉积过多、胶质增生、轴索硬化和严重的神经元丢失。苍白球内也可见铁沉积。有广泛的过度磷酸化的tau蛋白沉积的形式，神经元缠结，预缠结和神经元线程。此外，组织学研究和免疫印迹证实了混合的阿尔茨海默病3型和4型重复tau病理学。微管相关蛋白1A/1B-轻链3（LC 3）免疫印迹脑匀浆表明自噬活性，并可能支持WDR 45在自噬中的作用。这种疾病中广泛存在的阿尔茨海默型tau病理学表明，这应该被认为是一种tau蛋白病，并进一步支持了自噬受损可能在tau蛋白病中起作用的观点。本文的在线版本（doi：10.1186/s40478-015-0221-3）包含补充材料，可供授权用户使用。
Beta-propeller protein associated neurodegeneration (BPAN) is associated with mutations in the WD repeat domain 45 (WDR45) gene on chromosome Xp11 resulting in reduced autophagic flux. This study describes the clinical and neuropathological features of a female 51 year old BPAN case. The clinical history includes learning disability and progressive gait abnormalities since childhood followed by progressive dystonic features in young adulthood. Brain imaging revealed generalised brain atrophy and bilateral mineralisation of the globus pallidus and substantia nigra. The major pathological findings were observed in the substantia nigra with excess iron deposition, gliosis, axonal swellings and severe neuronal loss. Iron deposition was also observed in the globus pallidus. There was extensive hyperphosphorylated-tau deposition in the form of neurofibrillary tangles, pre-tangles and neuropil threads. Furthermore, histological studies and immunoblotting confirmed a mixed Alzheimer type 3-and 4-repeat tau pathology. Microtubule-associated protein 1A/1B-light chain 3 (LC3) immunoblotting of brain homogenates indicated autophagic activity and may support the role of WDR45 in autophagy. The widespread Alzheimer-type tau pathology in this disease indicates that this should be considered as a tauopathy and adds further support to the proposal that impaired autophagy may have a role in tauopathies. The online version of this article (doi:10.1186/s40478-015-0221-3) contains supplementary material, which is available to authorized users.
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