Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease.
Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease.
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DOI：
10.1002/mds.26172
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发表时间：
2015-06
影响因子：
8.6
通讯作者：
Leverenz, James B.
中科院分区：
文献类型：
--
作者：
Bekris, Lynn M.;Tsuang, Debby W.;Peskind, Elaine R.;Yu, Chang E.;Montine, Thomas J.;Zhang, Jing;Zabetian, Cyrus P.;Leverenz, James B.
最近的兴趣是发现传统上与阿尔茨海默病（AD）相关的某些CSF生物标志物，特别是淀粉样β蛋白（Aβ），在PD CSF中异常。本探索性研究旨在确定帕金森病（PD）患者淀粉样前体蛋白（APP）加工途径基因内的遗传变异是否与脑脊液（CSF）Aβ42水平相关。对PD（n=86）和对照（n=161）DNA进行基因分型，检测参与APP切割的9个基因（APP、ADAM 10、BACE 1、BACE 2、PSEN 1、PSEN 2、PEN 2、NCSTN和APH 1B）内的19个调节区标记单核苷酸多态性（SNP）。测试SNP基因型与CSF生物标志物和PD风险的相关性，同时调整年龄、性别和APOE ε4状态。观察到两个SNP（APP rs466448和APH1B rs2068143）与PD患者CSF Aβ42水平显著相关。相反，在对照组中观察到3个SNP（APP rs214484和rs2040273以及PSEN1 rs362344）与CSF Aβ42水平显著相关。这项探索性研究的结果表明，在APOE ε4非携带者中，APP SNP和APH 1B SNP与PD CSF Aβ42水平略有相关。产生的进一步假设包括CSF Aβ42水平降低部分由APP加工基因的遗传变异驱动。与其他神经退行性疾病（如AD）相比，有必要对这些发现与PD临床特征（包括认知障碍）之间的关系进行进一步研究。
Of recent interest is the finding that certain CSF biomarkers traditionally linked to Alzheimer’s disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine if genetic variation within the amyloid precursor protein (APP) processing pathway genes, correlate with cerebrospinal fluid (CSF) Aβ42 levels in Parkinson’s disease (PD). PD (n=86) and control (n=161) DNA were genotyped for 19 regulatory region tagging single nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN and APH1B) involved in the cleavage of APP. SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, gender, and APOE ε4 status. Significant correlation with CSF Aβ42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF Aβ42 levels in controls was observed for three SNPs (APP rs214484 and rs2040273 and PSEN1 rs362344). The results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ε4 non-carriers. Further hypotheses generated include that decreased CSF Aβ42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared to other neurodegenerative diseases, such as AD, are warranted.
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影响因子：
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作者：
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作者：
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通讯作者：
Knight, Jo