Immune blood biomarkers of Alzheimer disease patients

被引:48
作者
Avagyan, Hripsime [1 ]
Goldenson, Ben [1 ]
Tse, Eric [1 ]
Masoumi, Ava [1 ]
Porter, Verna [2 ,7 ,8 ]
Wiedau-Pazos, Martina [2 ,7 ,8 ]
Sayre, James [3 ]
Ong, Reno [1 ]
Mahanian, Michelle [1 ]
Koo, Patrick [1 ]
Bae, Susan [1 ]
Micic, Miodrag [4 ]
Liu, Philip T. [5 ]
Rosenthal, Mark J. [6 ]
Fiala, Milan [1 ]
机构
[1] Univ Calif Los Angeles, Orthopaed Hosp Res Ctr, Dept Orthopaed Surg, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA
[4] MP Biomed LLC, Santa Ana, CA 92707 USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Dermatol, Los Angeles, CA 90095 USA
[6] Greater LA VA Med Ctr, Dept Med, Los Angeles, CA 90095 USA
[7] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
[8] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA
关键词
Alzheimer disease; Biomarkers; Amyloid-beta; MGAT-III; Phagocytosis; Macrophages; INNATE IMMUNITY; AMYLOID-BETA; PLASMA; DIAGNOSIS; INFLAMMATION; CELLS;
D O I
10.1016/j.jneuroim.2009.02.015
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Alzheimer disease (AD) patients have an impairment of anti-amyloid-beta (A beta) innate immunity and a defect in immune gene transcription [Fiala, M., Liu, P.T., Espinosa-Jeffrey, A., Rosenthal, M.J., Bernard, G., Ringman, J.M., Sayre, J., Zhang, L, Zaghi, J., Dejbakhsh, S., Chiang, B., Hui, J., Mahanian, M., Baghaee, A., Hong, P., Cashman, J., 2007b. Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin. Proc. Natl. Acad. Sci. U. S. A. 104,12849-12854]. Early diagnosis is a cornerstone of preventive approaches to AD. Phospho-tau and A beta CSF levels are useful markers of neurodegeneration but not of a process leading to neurodegeneration. To detect an early biomarker of AD, we developed a flow cytometric test of A beta phagocytosis, which was 94% positive (<400 MFI units) in AD patients (mean age +/- SEM 77 + 2.2 years; mean score +/- SEM 198.6 +/- 25.5 MFI units) and 60% positive in MCI patients (77 +/- 5.6 years; 301 +/- 106 MFI units). Control subjects, active senior university professors, were 100% negative (74.2 +/- 4.2 years; 1348 +/- 174 MFI units). The test had a low specificity in older caregivers and older amyotrophic lateral sclerosis (ALS) patients. We also tested transcriptional regulation of the genes MGAT-III and Toll-like receptor-3 in macrophages. Macrophages of "Type I" patients (a majority of patients) showed gene down regulation at baseline and up regulation by curcuminoids: macrophages of "Type II" patients showed opposite responses. The results of flow cytometric testing suggest that normal A beta phagocytosis is associated with healthy cognition and lesser risk of AD. The significance of abnormal results in aged persons should be investigated by prospective studies to determine the risk of AD. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:67 / 72
页数:6
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