Abstract
It is becoming increasingly recognized that risk factors for vascular disease increase the risk for developing Alzheimer’s disease (AD), suggesting that the vasculature may be a contributing factor to the pathophysiology of AD. Furthermore, in the majority of AD cases, vascular deposits of β-amyloid (Aβ) peptides are observed in the condition known as cerebral amyloid angiopathy, suggesting that Aβ peptides may be biologically active at the vascular level. We present data demonstrating that low doses (in the nM range) of freshly solubilized Aβ peptides (1–40 and 1–42) greatly enhance the vasoconstriction induced by endothelin-1 (ET-1) in isolated, intact vessels. We also show that freshly solubilized Aβ peptides transduce vasoactivity via stimulation of a pro-inflammatory pathway involving activation of cytosolic phospholipase A2, cyclooxygenase-2, and 5-lipoxygenase. Our data demonstrate that soluble forms of Aß peptides (at doses similar to those found in AD patient plasma) are able to trigger a pro-inflammatory response in vessels, suggesting that, in AD, which has a significant inflammatory component, Aβ peptides may exert pro-inflammatory effects prior to deposition as insoluble Aβ aggregates.
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References
Ellis, R.J., Olichney, J.M., Thal, L.J., Mirra, S.S., Morris, J.C., Beekly, D., and Heyman, A. (1996) Cerebral amyloid angiopathy in the brains of patients with Alzheimer’s disease: the CERAD experience, Part XV, Neurology 46, 1592–1596.
Sparks, D.L. (1997) Coronary artery disease, hypertension, ApoE, and cholesterol: a link to Alzheimer’s disease? Ann. N.Y. Acad. Sci 826 128–146.
Crawford, F., Soto, C., Suo, Z., Fang, C., Parker, T., Sawar, A., Frangione, B., and Mullan, M. (1998a) Alzheimer’s (3-amyloid vasoactivity: identification of a novel ß-Amyloid conformational intermediate, FEBSLett. 436, 445–448.
Duara, R., Grady, C., Haxby, J., Sundaram, M., Cutler, N.R., Heston, L., Moore, A., Schlageter, N., Larson, S., and Rapoport, S.I. (1986) Positron emission tomography in Alzheimer’s disease, Neurology 36, 879–887.
Johnson, K.A., Mueller, S.T., Walshe, T.M., English, R.J., and Holman, B.L. (1987) Cerebral perfusion imaging in Alzheimer’s disease. Use of a single photon emission computed tomography and iofetamine hydrochloride I 123, Arch. Neurol. 44 165–168.
Friedland, R.P., Budinger, T.F., Ganz, E., Yano, Y., Mathis, C.A., Koss, B., Ober, B.A., Huesman, R.H., and Derenzo, S.E. (1983) Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with [18F]fluorodeoxyglucose, J. Comput. Assist. Tomogr. 7 590–598.
Iadecola, C., Zhang, F., Niwa, K., Eckman, C., Turner, S., Fischer, E., Younkin, S., Borchelt, D., Hsaio, K., and Carlson, G. (1999) SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein, Nat. Neurosci. 2 157–161.
Zhang, F., Eckman, C., Younkin, S., Hsiao, K.K., and ladecola, C. (1997) Increased susceptibility to ischemic brain damage in mice overexpressing the amyloid precursor protein, J. Neurosci. 17 7655–7661.
Jagust, W.J., Eberling, J.L., Reed, B.R., Mathis, C.A., and Budinger, T.F. (1997) Clinical studies of cerebral blood flow in Alzheimer’s disease, Ann. N. Y. Acad. Sci. 826 254–262.
Nagata, K., Buchan, R.J., Yokoyama, E., Kondoh, Y., Sato, M., Terashi, H., Sato, Y., Watahiki, Y., Senova, M., Hirata, Y., and Hatazawa, J. (1997) Misery perfusion with preserved vascular reactivity in Alzheimer’s disease, Ann. N. Y. Acad. Sci. 826 272–281.
Thomas, T., Thomas, G., McLendon, C., Sutton, T., and Mullan, M. (1996) ß-Amyloid mediated vasoactivity and vascular endothelial damage, Nature 380, 168–171.
Douglas, S.A. and Ohlstein, E.H. (1997) Signal transduction mechanisms mediating the vascular actions of endothelin, J. Vas. Res. 34 152–164.
Kuo, Y.M., Emmerling, M.R., Lampert, H.C., Hempelman, S.R., Kokjohn, T.A., Woods, A.S., Cotter, R.J., and Roher, A.E. (1999) High level of circulating 442 sequestered by plasma proteins in Alzheimer’s disease. Biochem. Biophys. Resch. Com. 257 787–791.
Moncada, S., Palmer, R., and Higgs, E. (1991) Nitric oxide: physiology, pathophysiology, and pharmacology, Pharmacol. Rev. 43 109–141.
Urmoneit, B., Prikulis, I. Wihl, G., D’Urso, D., Frank, R., Heeren, J., Beisiegel, U., and Prior, R. (1997) Cardiovascular smooth muscle cells internalize Alzheimer amyloid beta protein via a lipoprotein pathway: implications for cerebral amyloid angiopathy, Lab. Invest. 77 157–166.
Bonafi, L., Thomas, S.R., Hill, R.G., and Longmore, J. (1998) ß-Amyloid inhibits endothelial-dependent relaxations in rabbit isolated aorta: an interaction between superoxide radicals and nitric oxide?, Alzh. Reports 5 297–302.
Crawford, F., Suo, Z., Fang, C., and Mullan, M. (1998b) Characteristics of the in vitro vasoactivity of ß-amyloid peptides, Exp. Neurol. 150 159–168.
Paris, D. Parker, T.A., Town, T., Suo, Z., Fang, C., Humphrey, J., Crawford, F., and Mullan, M. (1998) Role of Peroxynitrite in the vasoactive and cytotoxic effects of Alzheimer’s ß-amyloid peptide, Exp. Neurol. 152 116–122.
Paris, D., Town, T., Parker, T.A., Humphrey, J., Tan, J., Crawford, F., and Mullan, M. (1999) Inhibition of Alzheimer’s ß-amyloid induced vasoactivity and pro-inflammatory response in microglia by a cGMP-dependent mechanism, Exp. Neurol. 157 211–221.
McGeer PL, Schulzer M, and 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.
Stewart, W.F., Kawas, C., Corrada, M., and Metter, E.J. (1997) Risk of Alzheimer’s disease and duration of NSAID use, Neurology 48, 626–632.
Rogers, J., Kirby, L.C., and Hempielman, S.R. (1993) Clinical trial of indomethacin in Alzheimer’s disease, Neurology 43, 1609–1611.
Coria, F., Moreno, A., Rubio, I., Garcia, M.A., Morato, E., and Mayor, F. (1993) The cellular pathology associated with Alzheimer ß-amyloid deposits in non-demented aged individuals, Neuropathol. Appl. Neurobiol. 19 261–268.
Griffin WST, Sheng JG, Roberts GW, and Mrak RE. (1995) Interleukin-1 expression in different plaque types in Alzheimer’s disease: significance in plaque evolution, J. Neuropathol. Exp Neurol. 54 276–281.
Itagaki S, McGeer PL, Akiyama H, Zhu S, and Selkoe D. (1989) Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease, J. Neuroimmunol. 24 173–182.
Lue, L.F., Brachova, L., Civin, W.H., and Rogers, J. (1996) Inflammation, Abeta deposition, and neurofibrillary tangle formation as correlates of Alzheimer’s disease neurodegeneration, J. Neuropathol. Exp. Neurol. 55 1083–1088.
Lio, Y.C., Reynolds, L.J., Balsinde, J., and Dennis, E.A. (1996) Irreversible inhibition of Ca(2+)-independent phospholipase A2 by methyl arachidonyl fluorophosphonate, Biochem. Biophys. Acta. 1302 55–60.
Wu, Y.L., Jiang, X.R., Newland, A.C., and Kelsey, S.M. (1998) Failure to activate cytosolic phospholipase A2 causes TNF resistance in human leukemic cells, J. Immunol. 160 5929–5935.
Gurwitz, J.G., Avorn, J., Bohn, R.L., Glynn, R.J., Monane, M., and Mogun, H. (1994) Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy, JAMA 272, 781–786.
Futaki, N., Takahashi, S., Yokoyama, M., Arai, I. Higuchi, S., and Otomo, S. (1994) NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro, Prostaglandins 47 55–59.
Lepley, R.A., Muskardin, D.T., and Fitzpatrick, F.A. (1996) Tyrosine kinase activity modulates catalysis and translocation of cellular 5-lipoxygenase, J. Biol. Chem. 271 61796184.
Kalaria., R.N. (1997) Cerebrovascular degeneration is related to amyloid-beta protein deposition in Alzheimer’s disease. Ann. N.Y. Acad. Sci. 826 263–271.
Kawai., M., Kalaria., R.N., Cras., P. Siedlak., S.L., Velasco, M.E., Shelton, E.R., Chan, H.W., Greenberg, B.D. Perry, G. (1993) Degeneration of vascular muscle cells in cerebral amyloid angiopathy of Alzheimer disease. Brain. Res. 623 142–146.
Kalaria, R.D., Bhatti, S., Lust, W., and Perry, G. (1993) The blood brain barrier and cerebral microcirculation in Alzheimer’s disease, Cerebrovas. Brain Metab. Rev. 4 226260.
Suo, Z., Humphrey, J., Kundtz, A., Sethi, F., Placzek, A., Crawford, F., and Mullan, M. (1998) Soluble Alzheimer’s (3-amyloid constricts the cerebral vasculature in vivo, Neurosci. Lett. 257 77–80.
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Paris, D., Town, T., Mullan, M. (2000). Vasoactivity of Amyloid β Peptides. In: Verbeek, M.M., de Waal, R.M.W., Vinters, H.V. (eds) Cerebral Amyloid Angiopathy in Alzheimer’s Disease and Related Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-1007-7_17
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DOI: https://doi.org/10.1007/978-94-017-1007-7_17
Publisher Name: Springer, Dordrecht
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