Cummings JL, Morstorf T, Zhong K. Alzheimer's disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther. 2014;6:37.
Bloom GS. Amyloid-beta and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol. 2014;71:505–8.
Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science. 1996;274:99–102.
Deane R, Bell RD, Sagare A, Zlokovic BV. Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease. CNS Neurol Disord: Drug Targets. 2009;8:16–30.
Park L, Zhou P, Koizumi K, El Jamal S, Previti ML, Van Nostrand WE, Carlson G, Iadecola C. Brain and circulating levels of Abeta1-40 differentially contribute to vasomotor dysfunction in the mouse brain. Stroke. 2013;44:198–204.
Tuppo EE, Arias HR. The role of inflammation in Alzheimer's disease. Int J Biochem Cell Biol. 2005;37:289–305.
Hensley K. Neuroinflammation in Alzheimer's disease: mechanisms, pathologic consequences, and potential for therapeutic manipulation. J Alzheimers Dis. 2010;21:1–14.
Mhatre M, Floyd RA, Hensley K. Oxidative stress and neuroinflammation in Alzheimer's disease and amyotrophic lateral sclerosis: common links and potential therapeutic targets. J Alzheimers Dis. 2004;6:147–57.
Ferretti MT, Cuello AC. Does a pro-inflammatory process precede Alzheimer's disease and mild cognitive impairment? Curr Alzheimer Res. 2011;8:164–74.
Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci. 2011;12:723–38.
Muoio V, Persson PB, Sendeski MM. The neurovascular unit—concept review. Acta Physiol (Oxf). 2014;210:790–8.
Keaney J, Campbell M. The dynamic blood-brain barrier. FEBS J. 2015;282:4067–79.
Redwine L, Mills PJ, Sada M, Dimsdale J, Patterson T, Grant I. Differential immune cell chemotaxis responses to acute psychological stress in Alzheimer caregivers compared to non-caregiver controls. Psychosom Med. 2004;66:770–5.
Zaghi J, Goldenson B, Inayathullah M, Lossinsky AS, Masoumi A, Avagyan H, Mahanian M, Bernas M, Weinand M, Rosenthal MJ, et al. Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy. Acta Neuropathol. 2009;117:111–24.
Grammas P, Martinez J, Miller B. Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases. Expert Rev Mol Med. 2011;13:e19.
Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015;16:358–72.
Birukova AA, Birukov KG, Smurova K, Adyshev D, Kaibuchi K, Alieva I, Garcia JG, Verin AD. Novel role of microtubules in thrombin-induced endothelial barrier dysfunction. FASEB J. 2004;18:1879–90.
Garcia JG. Concepts in microvascular endothelial barrier regulation in health and disease. Microvasc Res. 2009;77:1–3.
Wolfson RK, Chiang ET, Garcia JG. HMGB1 induces human lung endothelial cell cytoskeletal rearrangement and barrier disruption. Microvasc Res. 2011;81:189–97.
Nawaz MI, Mohammad G. Role of high-mobility group box-1 protein in disruption of vascular barriers and regulation of leukocyte-endothelial interactions. J Recept Signal Transduct Res. 2015;35:340–5.
Dumitriu IE, Baruah P, Manfredi AA, Bianchi ME, Rovere-Querini P. HMGB1: guiding immunity from within. Trends Immunol. 2005;26:381–7.
Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285:248–51.
Schiraldi M, Raucci A, Munoz LM, Livoti E, Celona B, Venereau E, Apuzzo T, De Marchis F, Pedotti M, Bachi A, et al. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med. 2012;209:551–63.
Venereau E, Schiraldi M, Uguccioni M, Bianchi ME. HMGB1 and leukocyte migration during trauma and sterile inflammation. Mol Immunol. 2013;55:76–82.
Mazarati A, Maroso M, Iori V, Vezzani A, Carli M. High-mobility group box-1 impairs memory in mice through both toll-like receptor 4 and receptor for advanced glycation end products. Exp Neurol. 2011;232:143–8.
Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304:1787–94.
Frank-Cannon TC, Alto LT, McAlpine FE, Tansey MG. Does neuroinflammation fan the flame in neurodegenerative diseases? Mol Neurodegener. 2009;4:47.
Clark IA, Vissel B. Amyloid beta: one of three danger-associated molecules that are secondary inducers of the proinflammatory cytokines that mediate Alzheimer's disease. Br J Pharmacol. 2015;172:3714–27.
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack Jr CR, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:263–9.
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:270–9.
Sajja RK, Green KN, Cucullo L. Altered Nrf2 signaling mediates hypoglycemia-induced blood-brain barrier endothelial dysfunction in vitro. PLoS One. 2015;10:e0122358.
Dhillon NK, Peng F, Bokhari S, Callen S, Shin SH, Zhu X, Kim KJ, Buch SJ. Cocaine-mediated alteration in tight junction protein expression and modulation of CCL2/CCR2 axis across the blood-brain barrier: implications for HIV-dementia. J Neuroimmune Pharmacol. 2008;3:52–6.
Van Dreden P, Rousseau A, Savoure A, Lenormand B, Fontaine S, Vasse M. Plasma thrombomodulin activity, tissue factor activity and high levels of circulating procoagulant phospholipid as prognostic factors for acute myocardial infarction. Blood Coagul Fibrinolysis. 2009;20:635–41.
Santilli F, Vazzana N, Bucciarelli LG, Davi G. Soluble forms of RAGE in human diseases: clinical and therapeutical implications. Curr Med Chem. 2009;16:940–52.
Yamagishi S, Matsui T. Soluble form of a receptor for advanced glycation end products (sRAGE) as a biomarker. Front Biosci (Elite Ed). 2010;2:1184–95.
Festoff BW, Li C, Woodhams B, Lynch S. Soluble thrombomodulin levels in plasma of multiple sclerosis patients and their implication. J Neurol Sci. 2012;323:61–5.
Fiuza C, Bustin M, Talwar S, Tropea M, Gerstenberger E, Shelhamer JH, Suffredini AF. Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. Blood. 2003;101:2652–60.
Conway EM. Thrombomodulin and its role in inflammation. Semin Immunopathol. 2012;34:107–25.
Leclerc E, Sturchler E, Vetter SW. The S100B/RAGE axis in Alzheimer's disease. Cardiovasc Psychiatry Neurol. 2010;2010:539581.
Yavuz BB, Dede DS, Yavuz B, Cankurtaran M, Halil M, Ulger Z, Cankurtaran ES, Aytemir K, Kabakci G, Haznedaroglu IC, Ariogul S. Potential biomarkers for vascular damage in Alzheimer's disease: thrombomodulin and von Willebrand factor. J Nutr Health Aging. 2010;14:439–41.
Delvaeye M, Conway EM. Coagulation and innate immune responses: can we view them separately? Blood. 2009;114:2367–74.
Guan JX, Sun SG, Cao XB, Chen ZB, Tong ET. Effect of thrombin on blood brain barrier permeability and its mechanism. Chin Med J (Engl). 2004;117:1677–81.
Bogatcheva NV, Garcia JG, Verin AD. Molecular mechanisms of thrombin-induced endothelial cell permeability. Biochemistry (Mosc). 2002;67:75–84.
Carmeliet P, De Strooper B. Alzheimer's disease: a breach in the blood-brain barrier. Nature. 2012;485:451–2.
Hartz AM, Bauer B, Soldner EL, Wolf A, Boy S, Backhaus R, Mihaljevic I, Bogdahn U, Klunemann HH, Schuierer G, Schlachetzki F. Amyloid-beta contributes to blood-brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy. Stroke. 2012;43:514–23.
Kook SY, Seok Hong H, Moon M, Mook-Jung I. Disruption of blood-brain barrier in Alzheimer disease pathogenesis. Tissue Barriers. 2013;1:e23993.
Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, et al. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature. 2012;485:512–6.
Sagare AP, Bell RD, Zhao Z, Ma Q, Winkler EA, Ramanathan A, Zlokovic BV. Pericyte loss influences Alzheimer-like neurodegeneration in mice. Nat Commun. 2013;4:2932.
Zhang J, Takahashi HK, Liu K, Wake H, Liu R, Maruo T, Date I, Yoshino T, Ohtsuka A, Mori S, Nishibori M. Anti-high mobility group box-1 monoclonal antibody protects the blood-brain barrier from ischemia-induced disruption in rats. Stroke. 2011;42:1420–8.
Okuma Y, Liu K, Wake H, Zhang J, Maruo T, Date I, Yoshino T, Ohtsuka A, Otani N, Tomura S, et al. Anti-high mobility group box-1 antibody therapy for traumatic brain injury. Ann Neurol. 2012;72:373–84.
Hori O, Brett J, Slattery T, Cao R, Zhang J, Chen JX, Nagashima M, Lundh ER, Vijay S, Nitecki D, et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J Biol Chem. 1995;270:25752–61.
van Beijnum JR, Buurman WA, Griffioen AW. Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis. 2008;11:91–9.
Bierhaus A, Humpert PM, Stern DM, Arnold B, Nawroth PP. Advanced glycation end product receptor-mediated cellular dysfunction. Ann N Y Acad Sci. 2005;1043:676–80.
Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, Stern DM, Nawroth PP. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berl). 2005;83:876–86.
Rochfort KD, Cummins PM. The blood-brain barrier endothelium: a target for pro-inflammatory cytokines. Biochem Soc Trans. 2015;43:702–6.
Liu S, Liu Y, Hao W, Wolf L, Kiliaan AJ, Penke B, Rube CE, Walter J, Heneka MT, Hartmann T, et al. TLR2 is a primary receptor for Alzheimer's amyloid beta peptide to trigger neuroinflammatory activation. J Immunol. 2012;188:1098–107.
Striggow F, Riek M, Breder J, Henrich-Noack P, Reymann KG, Reiser G. The protease thrombin is an endogenous mediator of hippocampal neuroprotection against ischemia at low concentrations but causes degeneration at high concentrations. Proc Natl Acad Sci U S A. 2000;97:2264–9.
Xi G, Reiser G, Keep RF. The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective? J Neurochem. 2003;84:3–9.
Suo Z, Wu M, Citron BA, Gao C, Festoff BW. Persistent protease-activated receptor 4 signaling mediates thrombin-induced microglial activation. J Biol Chem. 2003;278:31177–83.
Suo Z, Wu M, Citron BA, Palazzo RE, Festoff BW. Rapid tau aggregation and delayed hippocampal neuronal death induced by persistent thrombin signaling. J Biol Chem. 2003;278:37681–9.
Suo Z, Citron BA, Festoff BW. Thrombin: a potential proinflammatory mediator in neurotrauma and neurodegenerative disorders. Curr Drug Targets Inflamm Allergy. 2004;3:105–14.
Hirano K. The roles of proteinase-activated receptors in the vascular physiology and pathophysiology. Arterioscler, Thromb, Vasc Biol. 2007;27:27–36.
Bartha K, Domotor E, Lanza F, Adam-Vizi V, Machovich R. Identification of thrombin receptors in rat brain capillary endothelial cells. J Cereb Blood Flow Metab. 2000;20:175–82.
de Souza AW, Westra J, Limburg PC, Bijl M, Kallenberg CG. HMGB1 in vascular diseases: its role in vascular inflammation and atherosclerosis. Autoimmun Rev. 2012;11:909–17.
Fang P, Schachner M, Shen YQ. HMGB1 in development and diseases of the central nervous system. Mol Neurobiol. 2012;45:499–506.
Takata K, Takada T, Ito A, Asai M, Tawa M, Saito Y, Ashihara E, Tomimoto H, Kitamura Y, Shimohama S. Microglial amyloid-beta1-40 phagocytosis dysfunction is caused by high-mobility group box protein-1: implications for the pathological progression of Alzheimer's disease. Int J Alzheimers Dis. 2012;2012:685739.
Arai T, Miklossy J, Klegeris A, Guo JP, McGeer PL. Thrombin and prothrombin are expressed by neurons and glial cells and accumulate in neurofibrillary tangles in Alzheimer disease brain. J Neuropathol Exp Neurol. 2006;65:19–25.
Ito T, Kawahara K, Nakamura T, Yamada S, Nakamura T, Abeyama K, Hashiguchi T, Maruyama I. High-mobility group box 1 protein promotes development of microvascular thrombosis in rats. J Thromb Haemost. 2007;5:109–16.
Sasaki T, Liu K, Agari T, Yasuhara T, Morimoto J, Okazaki M, Takeuchi H, Toyoshima A, Sasada S, Shinko A, et al. Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson's disease. Exp Neurol. 2016;275(Pt 1):220–31.