Bekris Lynn M, Tsuang Debby W, Peskind Elaine R, Yu Chang E, Montine Thomas J, Zhang Jing, Zabetian Cyrus P, Leverenz James B
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Northwest Network Mental Illness Research, Education and Clinical Center (MIRECC), VA Puget Sound Health Care System, Seattle, Washington, USA.
Mov Disord. 2015 Jun;30(7):936-44. doi: 10.1002/mds.26172. Epub 2015 Mar 24.
Of recent interest is the finding that certain cerebrospinal fluid (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 whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD).
Parkinson's disease (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. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE ɛ4 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, rs2040273, and PSEN1 rs362344).
In addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ɛ4 noncarriers. 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 with other neurodegenerative diseases, such as AD, are warranted. © 2015 International Parkinson and Movement Disorder Society.
最近有研究发现，某些传统上与阿尔茨海默病（AD）相关的脑脊液（CSF）生物标志物，特别是淀粉样β蛋白（Aβ），在帕金森病（PD）患者的脑脊液中也存在异常。本探索性研究的目的是确定淀粉样前体蛋白（APP）加工途径基因内的遗传变异是否与帕金森病（PD）患者脑脊液中Aβ42水平相关。
对86例帕金森病患者和161例对照者的DNA进行基因分型，检测9个参与APP切割的基因（APP、ADAM10、BACE1、BACE2、PSEN1、PSEN2、PEN2、NCSTN和APH1B）内的19个调控区域标签单核苷酸多态性（SNP）。在调整年龄、性别和APOE ε4状态的同时，测试SNP基因型与脑脊液生物标志物和PD风险的相关性。
观察到两个SNP（APP rs466448和APH1B rs2068143）与PD患者脑脊液Aβ42水平显著相关。相反，在对照组中观察到三个SNP（APP rs214484、rs2040273和PSEN1 rs362344）与脑脊液Aβ42水平显著相关。
此外，本探索性研究结果表明，一个APP SNP和一个APH1B SNP与APOE ε4非携带者的PD脑脊液Aβ42水平存在微弱关联。由此产生的进一步假设包括，脑脊液Aβ42水平降低部分是由APP加工基因的遗传变异驱动的。有必要进一步研究这些发现与PD临床特征（包括认知障碍）之间的关系，并与其他神经退行性疾病（如AD）进行比较。©2015国际帕金森病和运动障碍协会。
