Inflammation plays an important role in the pathogenesis of Alzheimer's disease. This article reviews the results of prospective studies demonstrating that the level of systemic inflammation markers, particularly C-reactive protein and interleukin-6, can predict cognitive decline or dementia. The potential mechanisms linking systemic inflammatory molecules to cognitive decline are also discussed.
Akiyama H, Barger S, Barnum S, et al. Inflammation and Alzheimer's disease. Neurobiol Aging. 2000;21:383-421.
2.
Eikelenboom P, Bate C, Van Gool WA, etal;. Neuroinflammation in Alzheimer's disease and prion disease. Glia. 2002;40:232-239.
3.
Cagnin A, Brooks DJ, Kennedy AM, et al. In-vivo measurement of activated microglia in dementia. Lancet. 2001;358:461-467.
4.
Wenk GL. Inflammation in Alzheimer's disease: its role and an opportunity for therapy. Brain Aging. 2003;3:16-20.
5.
Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ. Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study. Ann Neurol. 2002;52:168-174.
6.
Weaver JD, Huang MH, Albert M, Harris T, Rowe JW, Seeman TE. Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology. 2002;59:371-378.
7.
Yaffe K, Lindquist K, Penninx BW, et al. Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology. 2003;61:76-80.
8.
Yaffe K, Kanaya A, Lindquist K, et al. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004;292:2237-2242.
9.
Engelhart MJ, Geerlings MI, Meijer J, et al. Inflammatory proteins in plasma and the risk of dementia: the Rotterdam Study. Arch Neurol. 2004;61:668-672.
10.
Dik MG, Jonker C, Hack CE, Smit JH, Comijs HC, Eikelenboom P. Serum inflammatory proteins and cognitive decline in older persons. Neurology. 2005;64:1371-1377.
11.
Perry VH. The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun. 2004;18:407-413.
12.
Perry VH, Newman TA, Cunningham C. The impact of systemic infection on the progression of neurodegenerative disease. Nat Rev Neurosci. 2003;4:103-112.
13.
Blasko I, Marx F, Steiner E, Hartmann T, Grubeck-Loebenstein B. TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs. FASEB J. 1999;13:63-68.
14.
Brugg B, Dubreuil YL, Huber G, Wollman EE, Delhaye-Bouchaud N, Mariani J. Inflammatory processes induce beta-amyloid precursor protein changes in mouse brain. Proc Natl Acad Sci U S A. 1995;92:3032-3035.
15.
Sheng JG, Bora SH, Xu G, Borchelt DR, Price DL, Koliatsos VE. Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid beta peptide in APPswe transgenic mice. Neurobiol Dis. 2003;14:133-145.
16.
Barrientos RM, Higgins EA, Biedenkapp JC, et al. Peripheral infection and aging interact to impair hippocampal memory consolidation. Neurobiol Aging. 2006;27:723-732.
17.
Krabbe KS, Reichenberg A, Yirmiya R, Smed A, Pedersen BK, Bruunsgaard H. Low-dose endotoxemia and human neuropsychological functions. Brain Behav Immun. 2005;19:453-460.
18.
Holmes C, El-Okl M, Williams AL, Cunningham C, Wilcockson D, Perry VH. Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2003;74:788-789.
19.
Guan Z, Fang J. Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats. Brain Behav Immun. 2006;20:64-71.
20.
Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003; 107:363-369.
Jialal I, Devaraj S, Venugopal SK. C-reactive protein: risk marker or mediator in atherothrombosis?Hypertension. 2004;44:6-11.
23.
Blackburn R, Giral P, Bruckert E, et al. Elevated C-reactive protein constitutes an independent predictor of advanced carotid plaques in dyslipidemic subjects. Arterioscler Thromb Vasc Biol. 2001;21:1962-1968.
24.
van der Meer IM, de Maat MP, Bots ML, et al. Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis: the Rotterdam Study. Arterioscler Thromb Vasc Biol. 2002;22:838-842.
25.
Cao JJ, Thach C, Manolio TA, et al. C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study. Circulation. 2003; 108:166-170.
26.
Wang TJ, Nam BH, Wilson PW, et al. Association of C-reactive protein with carotid atherosclerosis in men and women: the Framingham Heart Study. Arterioscler Thromb Vasc Biol. 2002;22:1662-1667.
27.
Rost NS, Wolf PA, Kase CS, et al. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke. 2001;32:2575-2579.
28.
Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973-979.
29.
Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836-843.
30.
Curb JD, Abbott RD, Rodriguez BL, et al. C-reactive protein and the future risk of thromboembolic stroke in healthy men. Circulation. 2003;107:2016-2020.
31.
Hoshi T, Kitagawa K, Yamagami H, Furukado S, Hougaku H, Hori M. Relations of serum high-sensitivity C-reactive protein and interleukin-6 levels with silent brain infarction. Stroke. 2005;36:768-772.
32.
van Dijk EJ, Prins ND, Vermeer SE, et al. C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation. 2005;112:900-905.