Re-Balancing of Inflammation and Aβ Immunity as a Therapeutic for Alzheimer's Disease-View from the Bedside

被引:13
作者
Fiala, Milan [1 ]
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA
关键词
Alzheimer's Disease; immune A hypothesis; nutrition; vitamin; 1; alpha; 25 (OH)(2) vitamin D3 eicosapentaenoic acid; curcuminoids; regulatory T cells; NITRIC-OXIDE SYNTHASE; BLOOD-BRAIN-BARRIER; AMYLOID-BETA; MICROGLIAL ACTIVATION; INNATE IMMUNITY; CYTOMEGALOVIRUS-INFECTION; COMPLEMENT ACTIVATION; VITAMIN-D; PHAGOCYTOSIS; MACROPHAGES;
D O I
10.2174/187152710791012044
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Morbidities of aging and Alzheimer's disease (AD) have been related to defective functions of both T cells and macrophages leading to brain amyloidosis and inflammation. In AD patients, "inflammaging" may be associated with an increase of incompetent memory T cells and inflammatory cytokines produced by macrophages, whereas defective clearance of amyloid-beta 1-42 (A beta) may be related to defective transcription of immune genes necessary for A beta phagocytosis, beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase and Toll-like receptors. However, AD shows considerable heterogeneity of disease manifestations and mechanisms. The approaches to re-balancing A beta immunity and inflammation are being pursued in transgenic animal models and peripheral blood mononuclear cells of patients. The regulatory signaling pathways of microglial phagocytosis and inflammation involving co-receptors and transforming growth factor-beta have been considerably clarified in animal studies. Natural immunostimulating therapies using vitamin D3 and curcuminoids have been developed in macrophages of AD patients. AD patients possess two types of macrophages: a majority has "Type I", which are improved by curcuminoids and vitamin D3; whereas a minority has "Type II" responding positively to vitamin D3 but not to curcuminoids. Other nutritional substances, such as plant polyphenols and omega-3 fatty acids, may inhibit inflammation and stimulate immunity. More invasive immune approaches involve A beta vaccine and cytokine antagonists. Increased inflammation may represent the "first hit", and defective transcription of immune genes the "second hit" in the pathogenesis of AD.
引用
收藏
页码:192 / 196
页数:5
相关论文
共 66 条
[1]   Inflammation and Alzheimer's disease [J].
Akiyama, H ;
Barger, S ;
Barnum, S ;
Bradt, B ;
Bauer, J ;
Cole, GM ;
Cooper, NR ;
Eikelenboom, P ;
Emmerling, M ;
Fiebich, BL ;
Finch, CE ;
Frautschy, S ;
Griffin, WST ;
Hampel, H ;
Hull, M ;
Landreth, G ;
Lue, LF ;
Mrak, R ;
Mackenzie, IR ;
McGeer, PL ;
O'Banion, MK ;
Pachter, J ;
Pasinetti, G ;
Plata-Salaman, C ;
Rogers, J ;
Rydel, R ;
Shen, Y ;
Streit, W ;
Strohmeyer, R ;
Tooyoma, I ;
Van Muiswinkel, FL ;
Veerhuis, R ;
Walker, D ;
Webster, S ;
Wegrzyniak, B ;
Wenk, G ;
Wyss-Coray, T .
NEUROBIOLOGY OF AGING, 2000, 21 (03) :383-421
[2]   Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons [J].
Almanzar, G ;
Schwaiger, S ;
Jenewein, B ;
Keller, M ;
Herndler-Brandstetter, D ;
Würzner, R ;
Schönitzer, D ;
Grubeck-Loebenstein, B .
JOURNAL OF VIROLOGY, 2005, 79 (06) :3675-3683
[3]  
ANNWEILER C, 2009, EUR J NEUROL
[4]   Immune blood biomarkers of Alzheimer disease patients [J].
Avagyan, Hripsime ;
Goldenson, Ben ;
Tse, Eric ;
Masoumi, Ava ;
Porter, Verna ;
Wiedau-Pazos, Martina ;
Sayre, James ;
Ong, Reno ;
Mahanian, Michelle ;
Koo, Patrick ;
Bae, Susan ;
Micic, Miodrag ;
Liu, Philip T. ;
Rosenthal, Mark J. ;
Fiala, Milan .
JOURNAL OF NEUROIMMUNOLOGY, 2009, 210 (1-2) :67-72
[5]  
Balin BJ, 2008, J ALZHEIMERS DIS, V13, P371
[6]   Dietary antioxidants and cardiovascular disease [J].
Blomhoff, R .
CURRENT OPINION IN LIPIDOLOGY, 2005, 16 (01) :47-54
[7]   n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases [J].
Calder, Philip C. .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 2006, 83 (06) :1505S-1519S
[8]   Signal transduction for inhibition of inducible nitric oxide synthase and cyclooxygenase-2 induction by capsaicin and related analogs in macrophages [J].
Chen, CW ;
Lee, ST ;
Wu, WT ;
Fu, WM ;
Ho, FM ;
Lin, WW .
BRITISH JOURNAL OF PHARMACOLOGY, 2003, 140 (06) :1077-1087
[9]   Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD [J].
Colton, Carol A. ;
Mott, Ryan T. ;
Sharpe, Hayley ;
Xu, Qing ;
Van Nostrand, William E. ;
Vitek, Michael P. .
JOURNAL OF NEUROINFLAMMATION, 2006, 3 (1)
[10]   Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients [J].
Damjanovic, Amanda K. ;
Yang, Yinhua ;
Glaser, Ronald ;
Kiecolt-Glaser, Janice K. ;
Nguyen, Huy ;
Laskowski, Bryon ;
Zou, Yixiao ;
Beversdorf, David Q. ;
Weng, Nan-ping .
JOURNAL OF IMMUNOLOGY, 2007, 179 (06) :4249-4254