Document Detail

Immune blood biomarkers of Alzheimer disease patients.
MedLine Citation:
PMID:  19329192     Owner:  NLM     Status:  MEDLINE    
Alzheimer disease (AD) patients have an impairment of anti-amyloid-beta (Abeta) 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 Abeta 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 Abeta 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 Abeta 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.
Hripsime Avagyan; Ben Goldenson; Eric Tse; Ava Masoumi; Verna Porter; Martina Wiedau-Pazos; James Sayre; Reno Ong; Michelle Mahanian; Patrick Koo; Susan Bae; Miodrag Micic; Philip T Liu; Mark J Rosenthal; Milan Fiala
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-28
Journal Detail:
Title:  Journal of neuroimmunology     Volume:  210     ISSN:  1872-8421     ISO Abbreviation:  J. Neuroimmunol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-18     Completed Date:  2009-07-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8109498     Medline TA:  J Neuroimmunol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  67-72     Citation Subset:  IM    
Department of Orthopaedic Surgery, UCLA Orthopaedic Hospital Research Center, Los Angeles, CA 90095, United States.
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MeSH Terms
Aged, 80 and over
Alzheimer Disease / diagnosis,  immunology,  metabolism*
Amyloid beta-Protein / analysis,  metabolism*
Biological Markers / analysis,  metabolism
Brain / immunology,  metabolism*,  physiopathology
Early Diagnosis
Encephalitis / diagnosis,  immunology,  metabolism*
Flow Cytometry / methods*
Gene Expression Regulation / immunology
Macrophages / immunology,  metabolism
Middle Aged
N-Acetylglucosaminyltransferases / genetics
Phagocytosis / immunology*
Predictive Value of Tests
Reproducibility of Results
Sensitivity and Specificity
Toll-Like Receptor 3 / genetics
Grant Support
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Biological Markers; 0/TLR3 protein, human; 0/Toll-Like Receptor 3; EC 2.4.1.-/N-Acetylglucosaminyltransferases; EC,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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