Abstract
Alzheimer’s disease is an age-dependent neurodegenerative disorder characterized by loss of neurons, synaptic degeneration, senile plaques and neurofibrillary tangles. Besides these hallmarks, increased accumulation of activated microglia, astrocytes and leukocytes adhering to postcapillary venules are observed in the affected brain areas, suggesting the presence of an ongoing inflammatory process. As neuroinflammation triggers the activation of peripheral immune system, many studies have analyzed circulating inflammatory biomarkers, including basal or stimulated levels of cytokines and related molecules in blood of Alzheimer’s patients, but with conflicting results. Platelets are an important source of amyloid-ß (Aß) in the circulatory system and play an important pro-inflammatory role. Upon activation, they adhere to leukocytes and endothelial cells by means of adhesive proteins like P-selectin, platelet endothelial cell adhesion molecule-1 (PECAM) and intercellular adhesion molecule-1 and -2 (ICAM-1 and -2) and secrete inflammatory mediators (chemokines, interleukins). In addition, platelets contain important enzymes involved in inflammatory intermediary synthesis like phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2), and recent reports demonstrated significant changes in platelet levels and activities in Alzheimer’s disease. Thus, as platelets represent an important link between Aß deposition and inflammatory reactions especially at endothelial level, they can be considered a valuable cellular model to evaluate potential peripheral inflammatory biomarkers in Alzheimer’s disease.
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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 WS, Hampel H, Hull M, Landreth G, Lue L, 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 (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421
Bermejo P, Martín-Aragón S, Benedí J, Susín C, Felici E, Gil P, Ribera JM, Villar AM (2008) Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer’s disease. Immunol Lett 117:198–202
Bonotis K, Krikki E, Holeva V, Aggouridaki C, Costa V, Baloyannis S (2008) Systemic immune aberrations in Alzheimer’s disease patients. J Neuroimmunol 193:183–187
Borroni B, Perani D, Broli M, Colciaghi F, Garibotto V, Paghera B, Agosti C, Giubbini R, Di Luca M, Padovani A (2005) Pre-clinical diagnosis of Alzheimer disease combining platelet amyloid precursor protein ratio and rCBF spect analysis. J Neurol 252:1359–1362
Borroni B, Agosti C, Marcello E, Di Luca M, Padovani A (2010) Blood cell markers in Alzheimer disease: amyloid precursor protein form ratio in platelets. Exp Gerontol 45:53–56
Casoli T, Di Stefano G, Giorgetti B, Balietti M, Recchioni R, Moroni F, Marcheselli F, Bernardini G, Fattoretti P, Bertoni-Freddari C (2008) Platelet as a physiological model to investigate apoptotic mechanisms in Alzheimer beta-amyloid peptide production. Mech Ageing Dev 129:154–162
Chen M, Inestrosa NC, Ross GS, Fernandez HL (1995) Platelets are the primary source of amyloid beta-peptide in human blood. Biochem Biophys Res Commun 213:96–103
Cupello A, Favale E, Audenino D, Scarrone S, Gastaldi S, Albano C (2005) Decrease of serotonin transporters in blood platelets after epileptic seizures. Neurochem Res 30:425–428
De Luigi A, Fragiacomo C, Lucca U, Quadri P, Tettamanti M, Grazia De Simoni M (2001) Inflammatory markers in Alzheimer’s disease and multi-infarct dementia. Mech Ageing Dev 122:1985–1995
Del Conde I, Crúz MA, Zhang H, López JA, Afshar-Kharghan V (2005) Platelet activation leads to activation and propagation of the complement system. J Exp Med 201:871–879
Fiala M, Liu QN, Sayre J, Pop V, Brahmandam V, Graves MC, Vinters HV (2002) Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer’s disease brain and damage the blood-brain barrier. Eur J Clin Invest 32:360–371
Galimberti D, Schoonenboom N, Scarpini E, Scheltens P, Dutch-Italian Alzheimer research Group (2003) Chemokines in serum and cerebrospinal fluid of Alzheimer’s disease patients. Ann Neurol 53:547–548
Gattaz WF, Forlenza OV, Talib LL, Barbosa NR, Bottino CM (2004) Platelet phospholipase A(2) activity in Alzheimer’s disease and mild cognitive impairment. J Neural Transm 111:591–601
Giri R, Shen Y, Stins M, Du Yan S, Schmidt AM, Stern D, Kim KS, Zlokovic B, Kalra VK (2000) Beta-amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1. Am J Physiol Cell Physiol 279:C1772–C1781
Gnatenko DV, Dunn JJ, McCorkle SR, Weissmann D, Perrotta PL, Bahou WF (2003) Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood 101:2285–2293
Halliday G, Robinson SR, Shepherd C, Kril J (2000) Alzheimer’s disease and inflammation: a review of cellular and therapeutic mechanisms. Clin Exp Pharmacol Physiol 27:1–8
Iarlori C, Gambi D, Gambi F, Lucci I, Feliciani C, Salvatore M, Reale M (2005) Expression and production of two selected beta-chemokines in peripheral blood mononuclear cells from patients with Alzheimer’s disease. Exp Gerontol 40:605–611
Klinger MH (1997) Platelets and inflammation. Anat Embryol (Berl) 196:1–11
Krzystanek E, Krzystanek M, Opala G, Trzeciak HI, Siuda J, Małecki A (2007) Platelet phospholipase A2 activity in patients with Alzheimer’s disease, vascular dementia and ischemic stroke. J Neural Transm 114:1033–1039
Lee KS, Chung JH, Lee KH, Shin MJ, Oh BH, Hong CH (2008) Bioplex analysis of plasma cytokines in Alzheimer’s disease and mild cognitive impairment. Immunol Lett 121:105–109
Li QX, Whyte S, Tanner JE, Evin G, Beyreuther K, Masters CL (1998) Secretion of Alzheimer’s disease Abeta amyloid peptide by activated human platelets. Lab Invest 78:461–469
Licastro F, Pedrini S, Caputo L, Annoni G, Davis LJ, Ferri C, Casadei V, Grimaldi LM (2000) Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer’s disease: peripheral inflammation or signals from the brain? J Neuroimmunol 103:97–102
McGeer PL, Schulzer M, McGeer EG (1996) Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology 47:425–432
Munnix IC, Cosemans JM, Auger JM, Heemskerk JW (2009) Platelet response heterogeneity in thrombus formation. Thromb Haemost 102:1149–1156
Nagele RG, D’Andrea MR, Lee H, Venkataraman V, Wang HY (2003) Astrocytes accumulate A beta 42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res 971:197–209
Nielsen HM, Londos E, Minthon L, Janciauskiene SM (2007) Soluble adhesion molecules and angiotensin-converting enzyme in dementia. Neurobiol Dis 26:27–35
Nuutinen T, Suuronen T, Kauppinen A, Salminen A (2009) Clusterin: a forgotten player in Alzheimer’s disease. Brain Res Rev 61:89–104
Prodan CI, Ross ED, Vincent AS, Dale GL (2007) Coated-platelets are higher in amnestic versus nonamnestic patients with mild cognitive impairment. Alzheimer Dis Assoc Disord 21:259–261
Prodan CI, Ross ED, Vincent AS, Dale GL (2009) Differences in coated-platelet production between frontotemporal dementia and Alzheimer disease. Alzheimer Dis Assoc Disord 23:234–237
Rainesalo S, Keranen T, Saransaari P, Honkaniemi J (2005) GABA and glutamate transporters are expressed in human platelets. Brain Res Mol Brain Res 141:161–165
Sevush S, Jy W, Horstman LL, Mao WW, Kolodny L, Ahn YS (1998) Platelet activation in Alzheimer disease. Arch Neurol 55:530–536
Sihlbom C, Davidsson P, Sjögren M, Wahlund LO, Nilsson CL (2008) Structural and quantitative comparison of cerebrospinal fluid glycoproteins in Alzheimer’s disease patients and healthy individuals. Neurochem Res 33:1332–1340
Song DK, Im YB, Jung JS, Cho J, Suh HW, Kim YH (2001) Central beta-amyloid peptide-induced peripheral interleukin-6 responses in mice. J Neurochem 76:1326–1335
Suo Z, Tan J, Placzek A, Crawford F, Fang C, Mullan M (1998) Alzheimer’s beta-amyloid peptides induce inflammatory cascade in human vascular cells: the roles of cytokines and CD40. Brain Res 807:107–110
Zarbock A, Polanowska-Grabowska RK, Ley K (2007) Platelet-neutrophil-interactions: linking hemostasis and inflammation. Blood Rev 21:99–111
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Casoli, T., Di Stefano, G., Balietti, M. et al. Peripheral inflammatory biomarkers of Alzheimer’s disease: the role of platelets. Biogerontology 11, 627–633 (2010). https://doi.org/10.1007/s10522-010-9281-8
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DOI: https://doi.org/10.1007/s10522-010-9281-8