摘要
介绍:这项研究检测了常染色体显性阿尔茨海默病(ADAD)突变携带者(MC)和非携带者(NC)之间120KDa 到110KDa血小板淀粉样前体蛋白(APP) 的异构体比率(APPr)。 先前两项研究报道ADAD MC 和NC间的APPr没有存在明显差异,这可能归因于这两项研究的采用的小样本数。本研究检测了较大样本中MC和NC的APPr. 此外我们调查了源于显性遗传性阿尔茨海默病网络(DIAN)研究的一个小子集,以研究APPr是否与神经影像数据、神经心理学数据和脑脊髓液生物标记物相关。 方法:采用蛋白质印迹法定量APPr。采用单变量一般线性模型比较15个MC(有症状的和无症状的)和12个NC。所有参与者进项了神经影像和神经心理学测试,使用皮尔逊相关系数(r)发现这些指标与APPr相关。结果:与NC组相比,MC组的APPr较低(p=0.03),而简易精神状态检查量表(MMSE)得分没有明显差异 (p>0.1)。并且,APPr与尾状核淀粉样蛋白成像(r=-0.505; p<0.05) 和楔前叶(r=-0.510; p<0.05)呈反负相关。结论:与NC组相比,ADAD MC组的APPr较低, 与脑内淀粉样负荷呈负相关,先于认知健康方面的显著差异。然而,使用APPr作为生物标记物仍需进一步的探究。
关键词: 阿尔茨海默病,淀粉样前体蛋白,生物标记物,神经心理学测试,匹兹堡化合物B,血小板
Current Alzheimer Research
Title:Decreased Platelet APP Isoform Ratios in Autosomal Dominant Alzheimer’s Disease: Baseline Data from a DIAN Cohort Subset
Volume: 12 Issue: 2
Author(s): Pratishtha Chatterjee, Veer B. Gupta, Anne M. Fagan, Mateusz S. Jasielec, Chengjie Xiong, Hamid R. Sohrabi, Satvinder Dhaliwal, Kevin Taddei, Pierrick Bourgeat, Belinda M. Brown, Tammie Benzinger, Randall J. Bateman, John C. Morris and Ralph N. Martins
Affiliation:
关键词: 阿尔茨海默病,淀粉样前体蛋白,生物标记物,神经心理学测试,匹兹堡化合物B,血小板
摘要: Introduction: This study examines platelet amyloid precursor protein (APP) isoform ratios of 120KDa to 110KDa (APPr) between mutation carriers (MC) carrying a mutation for autosomal dominant Alzheimer’s disease (ADAD) and non-carriers (NC). Two previous studies reported no significant difference in APPr between ADAD MC and NC, which may have been due to the small sample size in both studies. The current study examines APPr in MC versus NC in a larger sample. In addition, it investigated whether APPr correlate with neuroimaging data, neuropsychological data and cerebrospinal fluid biomarkers in a cohort subset derived from the Dominantly Inherited Alzheimer Network (DIAN) study. Methods: APPr were quantified by western blotting. Fifteen MC (symptomatic and asymptomatic) were compared against twelve NC using univariate general linear model. All participants underwent neuroimaging and neuropsychological testing which were correlated with APPr using Pearson’s correlation coefficient (r). Results: APPr were lower in MC compared to NC (p=0.003) while Mini-Mental State Examination (MMSE) scores were not significantly different (p>0.1). Furthermore, APPr inversely correlated with amyloid imaging in the Caudate Nucleus (r=-0.505; p<0.05) and Precuneus (r=-0.510; p<0.05). Conclusion: APPr are lower in ADAD MC compared to NC, and inversely correlated with brain amyloid load prior to significant differences in cognitive health. However, the use of APPr as a biomarker needs to be explored further.
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Pratishtha Chatterjee , Veer B. Gupta , Anne M. Fagan , Mateusz S. Jasielec , Chengjie Xiong , Hamid R. Sohrabi , Satvinder Dhaliwal , Kevin Taddei , Pierrick Bourgeat , Belinda M. Brown , Tammie Benzinger , Randall J. Bateman , John C. Morris and Ralph N. Martins , Decreased Platelet APP Isoform Ratios in Autosomal Dominant Alzheimer’s Disease: Baseline Data from a DIAN Cohort Subset, Current Alzheimer Research 2015; 12 (2) . https://dx.doi.org/10.2174/1567205012666150204125732
DOI https://dx.doi.org/10.2174/1567205012666150204125732 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
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Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
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