Blood-Derived Plasma Protein Biomarkers for Alzheimer's Disease in Han Chinese.

Zaohuo Cheng,Fuquan Zhang,Tao Wang,Shifu Xiao,Jiajun Yin,Hongwei Yuan,Zhiqiang Wang,Xiaowei Liu,Chunhui Jin,Yue Wu

doi:10.3389/fnagi.2018.00414

Abstract

It is well known that Alzheimer’s disease (AD) is one of the most common progressive neurodegenerative diseases; it begins gradually, and therefore no effective medicine is administered in the beginning. Thus, early diagnosis and prevention of AD are crucial. The present study focused on comparing the plasma protein changes between patients with AD and their healthy counterparts, aiming to explore a specific protein panel as a potential biomarker for AD patients in Han Chinese. Hence, we recruited and collected plasma samples from 98 AD patients and 101 elderly healthy controls from Wuxi and Shanghai Mental Health Centers. Using a Luminex assay, we investigated the expression levels of fifty plasma proteins in these samples. Thirty-two out of 50 proteins were found to be significantly different between AD patients and healthy controls (P < 0.05). Furthermore, an eight-protein panel that included brain-derived neurotrophic factor (BDNF), angiotensinogen (AGT), insulin-like growth factor binding protein 2 (IGFBP-2), osteopontin (OPN), cathepsin D, serum amyloid P component (SAP), complement C4, and prealbumin (transthyretin, TTR) showed the highest determinative score for AD and healthy controls (all P = 0.00). In conclusion, these findings suggest that a combination of eight plasma proteins can serve as a promising diagnostic biomarker for AD with high sensitivity and specificity in Han Chinese populations; the eight plasma proteins were proven important for AD diagnosis by further cross-validation studies within the AD cohort.

Highlights

The Centers for Disease Control and Prevention in the United States reported a 54.5% increase from the 1999 rate of 16.5 deaths per 100,000 patients with Alzheimer’s disease (AD) (Taylor et al, 2017), which is one of the most common progressive neurodegenerative diseases and is characterized by the interaction of both genetic and environmental factors, resulting in memory dysfunction and behavioral changes (Hooli and Tanzi, 2009)
We performed a stepwise discriminant function analysis to further determine how effectively AD patients and healthy controls can be distinguished based on the expressed protein levels and to assess the differential contribution to the diagnosis
Of the 32 significant plasma markers, a feature group of eight most discriminative proteins, including brain-derived neurotrophic factor (BDNF), angiotensinogen (AGT), insulinlike growth factor binding protein 2 (IGFBP-2), osteopontin (OPN), cathepsin D, serum amyloid P component (SAP), complement C4, and prealbumin, was sorted out by stepwise discriminant analysis (Table 3, all P = 0.00), indicating their potential contributions to diagnosis. To detect whether this 8-protein panel was efficient in differentiating AD from healthy controls, we carried out both original- and cross-validation, correctly classifying 86.7 and 84.7% of the cases, respectively (Table 4)

Summary

Introduction

The Centers for Disease Control and Prevention in the United States reported a 54.5% increase from the 1999 rate of 16.5 deaths per 100,000 patients with Alzheimer’s disease (AD) (Taylor et al, 2017), which is one of the most common progressive neurodegenerative diseases and is characterized by the interaction of both genetic and environmental factors, resulting in memory dysfunction and behavioral changes (Hooli and Tanzi, 2009). In 2013, the number of older people in China was almost 200 million, and the proportion of the population that was aged 65 years and older increased to 14.3% (Sun et al, 2015). The World Alzheimer Report 2015 updated the estimates of the global prevalence, China is the region with the most people living with dementia (9.5 million), and the prevalence for the population aged 60 and older is 6.19% Preclinical Alzheimer’s, the newly defined disease stage, demonstrates that brain changes are progressively initiated 10 to 20 years before the onset of dementia symptoms (Bateman et al, 2012). Previous studies have demonstrated plasma protein profiles may be a valuable diagnostic biomarker for the early stage of AD, the findings have not been widely replicated in different races (Kiddle et al, 2014; Shi et al, 2018)

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Results

Discussion

Conclusion