Biomarkers of inflammation and amyloid-beta phagocytosis in patients at risk of Alzheimer disease.
The ultimate goal of diagnostic research is a blood test detecting the risk of Alzheimer disease (AD) before neuronal damage develops. Current amyloid-beta (Abeta) tests do not detect the process leading to neurodegeneration. Novel immunologic and proteomics tests are based on aberrant appearance of inflammatory cytokines in the CSF and other protein biomarkers in the CSF or blood, and immune biomarkers of peripheral blood mononuclear cells (PBMC's). Cytokines, chemokines, complement factors, serum amyloid P component, and signaling proteins in the CSF or blood may be a rich source of diagnostic biomarkers, but the power of these tests will need to be examined in prospective studies. Recently-described flow cytometric test of defective Abeta phagocytosis detects patients with AD with a high sensitivity and specificity in distinct populations (confirmed AD patients vs. active University professors), but further experience is necessary for its use in general population at risk of AD. The analysis of the transcriptome of peripheral blood mononuclear cells "stressed" by Abeta is beginning to unravel the relations between specific pathways and AD. Thus novel diagnostic tests may provide biomarkers for pre-clinical detection, clarification of progression from MCI to AD, and follow-up of patients in clinical trials of immunostimulating therapies.
Fiala
Milan
M
Departments of Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA. fiala@mednet.ucla.edu
Veerhuis
Robert
R
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D015415:Biomarkers
Neurology. 2005 May 10;64(9):1563-72
15883317
J Neurosci. 2008 Jul 2;28(27):6926-37
18596167
Glia. 2009 Jul;57(9):978-88
19062178
Neurol Sci. 2006 Apr;27(1):33-9
16688597
JAMA. 2003 Apr 23-30;289(16):2094-103
12709467
Neurobiol Aging. 1996 Sep-Oct;17(5):673-80
8892339
Acta Neuropathol. 2009 Feb;117(2):111-24
19139910
Neurobiol Aging. 2009 Nov;30(11):1885-9
18378357
Subcell Biochem. 2005;38:129-45
15709476
Brain. 2006 Nov;129(Pt 11):3042-50
17071923
Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12849-54
17652175
Lancet Neurol. 2003 Oct;2(10):605-13
14505582
Arch Neurol. 2007 Mar;64(3):366-70
17353378
Nat Med. 2007 Nov;13(11):1359-62
17934472
Neurobiol Aging. 2000 May-Jun;21(3):383-421
10858586
J Alzheimers Dis. 2009;17(3):703-17
19433889
Ann Neurol. 2000 Apr;47(4):430-9
10762153
Int J Dev Neurosci. 2006 Apr-May;24(2-3):157-65
16384684
J Alzheimers Dis. 2006 Aug;9(3):293-348
16914840
J Neuroinflammation. 2006 Sep 27;3:27
17005052
J Neuroinflammation. 2005 Nov 21;2:27
16300681
J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1200-5
12933918
Neurobiol Dis. 2009 Aug;35(2):128-40
19010417
J Neurosci. 2005 Nov 23;25(47):10884-93
16306401
J Neurosci. 2009 Mar 18;29(11):3603-12
19295164
Dement Geriatr Cogn Disord. 2008;26(6):522-7
19052452
Neurobiol Aging. 2008 May;29(5):669-75
17208336
Neurobiol Aging. 2005 Mar;26(3):341-7
15639312
Immunobiology. 2000 May;202(1):26-33
10879686
Curr Drug Targets CNS Neurol Disord. 2005 Jun;4(3):235-48
15975027
Proc Natl Acad Sci U S A. 2009 May 5;106(18):7619-23
19372378
Acta Neurol Scand. 2008 Jul;118(1):1-11
18279484
Ann Neurol. 2009 Feb;65(2):176-83
19260027
Neurosci Lett. 2007 Apr 6;416(1):87-91
17317005
J Neuroimmunol. 2009 May 29;210(1-2):67-72
19329192
Am J Pathol. 2007 Dec;171(6):1989-99
18055545
J Neurosci Res. 2002 Nov 1;70(3):462-73
12391607
Eur J Clin Invest. 2002 May;32(5):360-71
12027877
CNS Neurol Disord Drug Targets. 2009 Mar;8(1):16-30
19275634
Arch Neurol. 2007 Mar;64(3):343-9
17210801
J Alzheimers Dis. 2005 Jun;7(3):221-32; discussion 255-62
16006665
J Neurol. 2007 Dec;254(12):1666-75
17994313