常染色体显性阿尔茨海默病血小板APP 的异构体比率的降低：源于DIAN群子集的基线数据

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.

Cite this article as:

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