In vivo evidence of cortical amyloid deposition in the adult form of Niemann Pick type C
In vivo evidence of cortical amyloid deposition in the adult form of Niemann Pick type C
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DOI：
10.1016/j.heliyon.2019.e02776
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发表时间：
2019-11-01
期刊：
影响因子：
4
通讯作者：
Manganelli, Fiore
中科院分区：
文献类型：
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作者：
Esposito, Marcello;Dubbioso, Raffaele;Manganelli, Fiore
背景资料：C型尼曼匹克病（Niemann Pick disease type C，NPC）是一种溶酶体脂质沉积症，表现为内脏和神经功能损害，伴有认知功能下降。NPC中的神经变性与淀粉样蛋白β和异常tau聚集的沉积相关，类似于阿尔茨海默病（AD）。痴呆还与可以通过NPC和AD中的神经生理学程序检测到的皮质内回路异常有关。本研究的目的是寻找NPC认知障碍患者体内淀粉样蛋白沉积的证据，并根据与AD的相似性探讨痴呆的病理生理学。受NPC和认知能力下降影响的两姐妹篇接受了神经心理学测试、F-18- Florbetaben PET扫描和神经生理学方案，以通过经颅磁刺激（TMS）评估皮质兴奋性，结果：2例患者均表现为多域认知功能障碍，且SAI和SICI均异常。F-18- Florbetaben PET扫描显示NPC的认知功能障碍与皮质淀粉样蛋白沉积相关淀粉样蛋白成像数据，以及TMS研究中发现的特定异常，表明NPC和AD痴呆的潜在机制相似。
Background: Niemann Pick disease type C (NPC) is a lysosomal lipid storage disorder presenting visceral and neurological impairment with cognitive decline. Neurodegeneration in NPC is associated to deposition of amyloid-beta and abnormal tau aggregations likewise Alzheimer disease (AD). Dementia is also related to intracortical circuiting abnormalities that can be detected by neurophysiological procedures both in NPC and in AD. Aim of this study is to find the in vivo evidence of amyloid deposition in NPC patients with cognitive impairment and to investigate the pathophysiology of dementia according to similarities with AD.Methods: Two sisters affected by NPC and cognitive decline underwent neuropsychological tests, PET scans with F-18- Florbetaben and neurophysiological protocols to assess cortex excitability by means of transcranial magnetic stimulation (TMS), such as short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF).Results: Both patients presented a multidomain cognitive impairment F-18- Florbetaben uptake was detected in brain frontal areas, while SAI and SICI were abnormal in both patients.Discussion: Cognitive impairment in NPC is associated to cortical amyloid deposition as revealed by F-18- Florbetaben PET scan. Amyloid imaging data, together with specific abnormalities found at TMS studies, suggest similar mechanisms underlying NPC and AD dementia.