期刊
ACTA NEUROPATHOLOGICA
卷 125, 期 5, 页码 753-769出版社
SPRINGER
DOI: 10.1007/s00401-013-1096-7
关键词
Parkinson's disease; Multiple system atrophy; alpha-Synuclein; SNCA
资金
- Parkinson's UK
- Multiple System Atrophy Trust
- Alzheimer's Research UK
- Progressive Supranuclear Palsy (Europe) Association
- Reta Lila Weston Institute for Neurological Studies
- Government of Kuwait
- MRC
- DMRF
- Parkinson's disease foundation
- National Institute for Health Research (NIHR) Biomedical Research Unit in Dementia based at University College London Hospitals (UCLH), University College London (UCL)
- Wellcome Trust/MRC [WT089698]
- University of Sheffield
- MRC Protein Phosphorylation Unit at the University of Dundee
- MRC [G108/638, G1001253, MR/J004758/1, G0802760, MC_G1000735, G0701075] Funding Source: UKRI
- Medical Research Council [G0802760, G0701075, G1001253, MC_G1000735, G108/638, MR/J004758/1] Funding Source: researchfish
- Parkinson's UK [F-1002] Funding Source: researchfish
We report a British family with young-onset Parkinson's disease (PD) and a G51D SNCA mutation that segregates with the disease. Family history was consistent with autosomal dominant inheritance as both the father and sister of the proband developed levodopa-responsive parkinsonism with onset in their late thirties. Clinical features show similarity to those seen in families with SNCA triplication and to cases of A53T SNCA mutation. Post-mortem brain examination of the proband revealed atrophy affecting frontal and temporal lobes in addition to the caudate, putamen, globus pallidus and amygdala. There was severe loss of pigmentation in the substantia nigra and pallor of the locus coeruleus. Neuronal loss was most marked in frontal and temporal cortices, hippocampal CA2/3 subregions, substantia nigra, locus coeruleus and dorsal motor nucleus of the vagus. The cellular pathology included widespread and frequent neuronal alpha-synuclein immunoreactive inclusions of variable morphology and oligodendroglial inclusions similar to the glial cytoplasmic inclusions of multiple system atrophy (MSA). Both inclusion types were ubiquitin and p62 positive and were labelled with phosphorylation-dependent anti-alpha-synuclein antibodies In addition, TDP-43 immunoreactive inclusions were observed in limbic regions and in the striatum. Together the data show clinical and neuropathological similarities to both the A53T SNCA mutation and multiplication cases. The cellular neuropathological features of this case share some characteristics of both PD and MSA with additional unique striatal and neocortical pathology. Greater understanding of the disease mechanism underlying the G51D mutation could aid in understanding of alpha-synuclein biology and its impact on disease phenotype.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据