Gupta Veer B, Wilson Andrea C, Burnham Samantha, Hone Eugene, Pedrini Steve, Laws Simon M, Lim Wei Ling Florence, Rembach Alan, Rainey-Smith Stephanie, Ames David, Cobiac Lynne, Macaulay S Lance, Masters Colin L, Rowe Christopher C, Bush Ashley I, Martins Ralph N
Centre of Excellence in Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027 Australia ; McCusker Alzheimer's Research Foundation, Hollywood Medical Centre, 85 Monash Avenue, Suite 22, Nedlands, 6009 Australia.
CSIRO Computational Informatics, Preventative Health Flagship, 65 Brockway Road, Floreat, 6014 Australia.
Alzheimers Res Ther. 2015 Feb 20;7(1):16. doi: 10.1186/s13195-015-0105-6. eCollection 2015.
Alzheimer's disease (AD) is a growing socioeconomic problem worldwide. Early diagnosis and prevention of this devastating disease have become a research priority. Consequently, the identification of clinically significant and sensitive blood biomarkers for its early detection is very important. Apolipoprotein E (APOE) is a well-known and established genetic risk factor for late-onset AD; however, the impact of the protein level on AD risk is unclear. We assessed the utility of plasma ApoE protein as a potential biomarker of AD in the large, well-characterised Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) cohort.
Total plasma ApoE levels were measured at 18-month follow-up using a commercial bead-based enzyme-linked immunosorbent assay: the Luminex xMAP human apolipoprotein kit. ApoE levels were then analysed between clinical classifications (healthy controls, mild cognitive impairment (MCI) and AD) and correlated with the data available from the AIBL cohort, including but not limited to APOE genotype and cerebral amyloid burden.
A significant decrease in ApoE levels was found in the AD group compared with the healthy controls. These results validate previously published ApoE protein levels at baseline obtained using different methodology. ApoE protein levels were also significantly affected, depending on APOE genotypes, with ε2/ε2 having the highest protein levels and ε4/ε4 having the lowest. Plasma ApoE levels were significantly negatively correlated with cerebral amyloid burden as measured by neuroimaging.
ApoE is decreased in individuals with AD compared with healthy controls at 18-month follow-up, and this trend is consistent with our results published at baseline. The influence of APOE genotype and sex on the protein levels are also explored. It is clear that ApoE is a strong player in the aetiology of this disease at both the protein and genetic levels.
阿尔茨海默病（AD）在全球范围内是一个日益严重的社会经济问题。对这种毁灭性疾病的早期诊断和预防已成为研究重点。因此，识别具有临床意义且敏感的血液生物标志物以实现早期检测非常重要。载脂蛋白E（APOE）是晚发性AD一个广为人知且已确定的遗传风险因素；然而，蛋白质水平对AD风险的影响尚不清楚。我们在大规模、特征明确的澳大利亚衰老成像、生物标志物和生活方式研究（AIBL）队列中评估了血浆载脂蛋白E蛋白作为AD潜在生物标志物的效用。
在18个月随访时，使用基于磁珠的商业酶联免疫吸附测定法（Luminex xMAP人载脂蛋白试剂盒）测量血浆总载脂蛋白E水平。然后分析临床分类（健康对照、轻度认知障碍（MCI）和AD）之间的载脂蛋白E水平，并将其与AIBL队列中可得的数据相关联，这些数据包括但不限于APOE基因型和脑淀粉样蛋白负荷。
与健康对照相比，AD组中载脂蛋白E水平显著降低。这些结果验证了先前使用不同方法获得的基线时载脂蛋白E蛋白水平。载脂蛋白E蛋白水平也受到APOE基因型的显著影响，ε2/ε2的蛋白水平最高，ε4/ε4的最低。通过神经影像学测量，血浆载脂蛋白E水平与脑淀粉样蛋白负荷显著负相关。
在18个月随访时，与健康对照相比，AD患者的载脂蛋白E水平降低，且这一趋势与我们在基线时发表的结果一致。还探讨了APOE基因型和性别对蛋白水平的影响。显然，载脂蛋白E在该疾病的病因学中，在蛋白质和基因水平上都是一个重要因素。
