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| The value of exosomal ABCA1 protein in the diagnosis of Alzheimer′s disease |
| LIU Chengeng1 ZHI Yang2 LI Ying1,3 ZHAO Yue1 LU Yao1 WANG Peichang1 |
1.Department of Clinical Laboratory, Xuanwu Hospital, Capital Medcial University, Beijing 100053, China;
2.Department of Clinical Laboratory, Beijing Xicheng District Guangwai Hospital, Beijing 100055, China;
3.Department of Clinical Laboratory, PLA Air Force Medical Characteristic Center, Beijing 100142, China |
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Abstract Objective To preliminary study the value of exosome ABCA1 protein as a diagnostic marker for Alzheimer′s disease (AD) through mouse experiments and clinical specimen detection. Methods Cerebrospinal fluid (CSF) and serum exosomes of APP/PS1 AD model mice in nine-month-old group were extracted and analyzed by mass spectrometry and ABCA1 protein detected by enzyme linked immunosorbent assay (ELISA). After three, six, nine months old APP/PS1 mice cerebrospinal fluid exosomes were injected into the third ventricle of three-month-old wild type (WT) mice, serum and CSF of zero, two, four, six-hour-groups were detected respectively exosome ABCA1 level. Serum exosome ABCA1 levels were detected in 69 patients with subjective cognitive decline (SCD group), 43 patients with mild cognitive impairment (MCI group) and 35 patients with dementia (DAT group) and 30 cases of control group. Results The results of mass spectrometry and ELISA showed that the levels of CSF and ABCA1 protein in serum of APP/PS1 double transgenic mice in three-month-old group, six-month-old group and nine-month-old group were higher than those of WT mice at the same month age (P < 0.05). CSF and serum exosomes ABCA1 protein of APP/PS1 double transgenic mice in six-month-old group were significantly higher than those in three-month-old group (P < 0.05). CSF and serum exosomes ABCA1 protein in nine-month-old APP/PS1 double transgenic mice were significantly higher than those in six-month-old APP/PS1 double transgenic mice (P < 0.05). The serum level of ABCA1 protein in WT mice was significantly increased in two, four and six hour-groups after exosomes injection (P < 0.05), and the highest level was found in four-hour group. The levels of ABCA1 protein in CSF exosomes of WT mice were significantly decreased in two, four and six hour-group after exosomes injection (P < 0.05), and the lowest in six-hour-group. There was no significant difference in ABCA1 protein between SCD group and control group (P > 0.05). The level of ABCA1 protein in serum of MCI group and DAT group was significantly higher than that of control group (P < 0.05), and that of DAT group was significantly higher than that of MCI group (P < 0.05). When the cut-off value was 0.39, the sensitivity and specificity of ABCA1 protein was 72.5% and 75.4% respectively, when the cut-off value was 0.52, the sensitivity and specificity of ABCA1 protein was 70.1% and 69.2% respectively in the diagnose of MCI. The diagnostic efficiency of ABCA1 protein in MCI and DAT was significantly higher than that in SCD (P < 0.05). Conclusion ABCA1 exosomes can pass through the blood-brain barrier and reach the peripheral blood, which can be used as a candidate marker for AD diagnosis. However, more research data need to be accumulated in the diagnosis of SCD.
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