LRP10 变异携带者伴发痴呆的临床及病理表型。
Clinical and Pathological Phenotypes of LRP10 Variant Carriers with Dementia.
机构信息
Erasmus MC, University Medical Center Rotterdam, Department of Neurology and Alzheimer Center, Rotterdam, the Netherlands.
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam, the Netherlands.
出版信息
J Alzheimers Dis. 2020;76(3):1161-1170. doi: 10.3233/JAD-200318.
BACKGROUND
Rare variants in the low-density lipoprotein receptor related protein 10 gene (LRP10) have recently been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB).
OBJECTIVE
We searched for LRP10 variants in a new series of brain donors with dementia and Lewy pathology (LP) at autopsy, or dementia and parkinsonism without LP but with various other neurodegenerative pathologies.
METHODS
Sanger sequencing of LRP10 was performed in 233 donors collected by the Netherlands Brain Bank.
RESULTS
Rare, possibly pathogenic heterozygous LRP10 variants were present in three patients: p.Gly453Ser in a patient with mixed Alzheimer's disease (AD)/Lewy body disease (LBD), p.Arg151Cys in a DLB patient, and p.Gly326Asp in an AD patient without LP. All three patients had a positive family history for dementia or PD.
CONCLUSION
Rare LRP10 variants are present in some patients with dementia and different brain pathologies including DLB, mixed AD/LBD, and AD. These findings suggest a role for LRP10 across a broad neurodegenerative spectrum.
背景
低密度脂蛋白受体相关蛋白 10 基因（LRP10）的罕见变异最近与帕金森病（PD）和路易体痴呆（DLB）的病因有关。
目的
我们在尸检时具有路易体病理学（LP）的新一系列痴呆症和Lewy 病理学（LP）的脑供体或无 LP 但具有各种其他神经退行性病理学的痴呆症和帕金森病患者中寻找 LRP10 变体。
方法
对荷兰脑库收集的 233 名供体进行了 LRP10 的 Sanger 测序。
结果
在三名患者中存在罕见的，可能致病性的杂合 LRP10 变体：患有混合阿尔茨海默病（AD）/Lewy 体病（LBD）的患者中的 p.Gly453Ser、DLB 患者中的 p.Arg151Cys 和无 LP 的 AD 患者中的 p.Gly326Asp。所有三名患者均有痴呆症或 PD 的阳性家族史。
结论
在一些具有痴呆症和不同脑病理学的患者中存在罕见的 LRP10 变体，包括 DLB、混合 AD/LBD 和 AD。这些发现表明 LRP10 在广泛的神经退行性谱中起作用。
Zotero 插件