Immune blood biomarkers of Alzheimer disease patients.

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.