Abstract
Cerebral amyloid angiopathy (CAA) is an amyloid deposition in the wall of arteries and veins in the leptomeninges, and also in the arterioles and capillaries in the cortex. Major isoforms were Aβx−40 (Aβ40) and Aβx−42(43) (Aβ42). Immunohistochemical analysis revealed focal deposits of Aβ42 in the early stages of CAA in both meningeal and cortical vessels. In advanced stages of CAA, the entire vessel wall is labeled for both Aβ40 and Aβ42, and Aβ40 labeling is predominant. In advanced CAA, Aβ40 becomes partly soluble and diffuses out from the vessel walls after dipping the tissue sections in formic acid. The N-terminal of deposited Aβ varies due to proteolytic cleavage and processing. These findings are consistent in normal aged people and in disorders having CAA; i.e.sporadic AD, early-onset familial AD with both APP and presenilin mutations, Down syndrome and HCHWA-D. In an early stage, deposition of amyloid-associated proteins in the basement membrane precedes focal Aβ42 deposition. Initial Aβ42 deposits may be a seed for further massive deposition of Aβ40 (leading to advanced CAA) in both meningeal and cortical vessels.
Keywords
- Down Syndrome
- Cerebral Amyloid Angiopathy
- Cortical Vessel
- Severe Cerebral Amyloid Angiopathy
- Capillary Cerebral Amyloid Angiopathy
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References
Davis-Salinas, J., Saporito-Irwin, S.M., Cotman, C.W., van Nostrand, W.E. (1995) Amyloid a-protein induces its own production in cultured degenerating cerebrovascular smooth muscle cells. J. Neurochem. 65, 931–934.
Frackowiak, J., Zoltowska, A. and Wisniewski, H.M. (1994) Non-fibrillar 0-Amyloid protein is associated with smooth muscle cells of vessel walls in Alzheimer Disease. J. Neuropathol. Exp. Neurol. 53, 637–645.
Joachim, C.L., Duffy, L.K., Morris, J.H. and Selkoe, D.J. (1988) Protein chemical and immunocytochemical studies of meningovascular —amyloid protein in Alzheimer’s disease and normal aging. Brain Res. 474, 100–111.
Roher, A.E., Lowenson, J.D., Clarke, S., Woods, A.S., Cotter, R.J., Gowing, E and Ball, M.J. (1993) 0-Amyloid-(1–42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 10836–40.
Roher, A.E., Lowenson, J.D., Clarke, S., Wolkow, C., Wang, R., Cotter R.J., Readon I.M., Zurcher-Neely, H.A., Heinrikson, R.L., Ball, M.J. and Greenberg, B.D. (1993) Structural alterations in the peptide backbone of 0-amyloid core protein may account for its deposition and stability in Alzheimer’s disease. J. Biol. Chem. 268, 3072–83.
Yamaguchi, H., Yamazaki, T., Lemere, C.A., Frosch, M.P. and Selkoe, D.J. (1992) Beta amyloid is focally deposited within the outer basement membrane in the amyloid angiopathy of Alzheimer’s disease. An immunoelectron microscopic study. Am. J. Pathol. 141, 249–259.
Shinkai, Y., Yoshimura, M., Ito, Y., Odaka, A., Suzuki, N., Yanagisawa, K. and Ihara, Y. (1995) Amyloid 0-proteins 1–40 and 1–42(43) in the soluble fraction of extra-and intracranial blood vessels. Ann. Neurol. 38, 421–428.
Alonzo, N.C., Hyman, B.T., Rebeck, G.W. and Greenberg, S.M. (1998) Progression of cerebral amyloid angiopathy: accumulation of amyloid-040 in affected vessels. J. Neuropathol. Exp. Neurol. 57, 353–359.
Iwatsubo, T., Okada, A., Suzuki, N., Mizusawa, H., Nukina, N. and Ihara, Y. (1994) Visualization of Aß42(43) and A040 in senile plaques with end-specific Aß monoclonals: evidence that an initial deposited species is A042(43). Neuron 13, 45–53.
Mak, K., Yang, F., Vinters, H.V., Frautschy, S.A. and Cole, G.M. (1994) Polyclonals to 13-amyloid (1–42) identify most plaque and vascular deposits in Alzheimer cortex, but not striatum. Brain Res. 667, 138–142.
Yamaguchi, H., Sugihara, S., Ishiguro, K., Takashima, A. and Hirai, S. (1995) Immunohistochemical analysis of COOH-termini of amyloid beta protein (A13) using end-specific antisera for A1340 and A1342 in Alzheimer’s disease and normal aging. Amyloid: Int. J. Clin. Invest. 2, 7–16.
Lemere, C.A., Lopera, F., Kosik, K.S., Lendon, C.L., Ossa, J., Saido, T.C., Yamaguchi, H., Ruiz, A., Martinez, A., Madrigal, L., Hincapie, L., Arango, J.C., Anthony, D.C., Koo, E.H., Goate, A.M., Selkoe, D.J. and Arango, J.C. (1996) The E280A presenilin 1 Alzheimer mutation produces increased A1342 deposition and severe cerebellar pathology. Nat. Med. 2, 1146–1150.
Kalaria, R.N., Cohen, D.L., Greenberg, B.D., Savage, M.J., Bogdanovic, NE., Winblad B., Lannfelt, L. and Adern, A. (1996) Abundance of the longer A1342 in neocortical and cerebrovascular amyloid 13-deposits in Swedish familial Alzheimer’s disease and Down’s syndrome. Neuroreport 7, 1377–1381.
Tamaoka, A., Sawamura, N., Odaka, A, Suzuki, N., Mizusawa, H., Shiji, S. and Mori, H. (1995) Amyloid 13-protein 1–42/43 (A131–42/3) in cerebellar difuse plaques: enzyme-linked immunosorbent assay and immunohistochemical study. Brain Res. 697, 151–156.
Suzuki, N., Iwatsubo, T., Odaka, A., Ishibashi, Y., Kitada, C. and Ihara, Y. (1994) High tissue content of soluble 01.40 is linked to cerebral amyloid angiopathy. Am. J. Pathol. 145, 452–460.
Suzuki, N., Cheung, T.T., Cai, X.D., Odaka, A., Otvos, L. Jr., Eckman, C., Golde, T.E., Younkin, S.G. (1994) An increased percentage of long amyloid 13 protein secreted by familial amyloid beta protein precursor (13APP717) mutants. Science 264, 1336–1340.
Mann, D.M.A., Iwatsubo, T., Ihara, Y., Cairns, N.J., Lantos, P.L., Bogdanovic, N., Lannfelt, L., Winblad, B., Maat-Schieman, M.L.C. and Rossor, M.N. (1996) Predominant deposition of amyloid-042(43) in plaques in cases of Alzheimer’s disease and hereditary cerebral hemorrhage associated with mutations in the amyloid precursor protein gene. Am. J. Pathol. 148, 1257–1266.
Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A.Y., Seubert, P., VigoPelfrey, C., Lieberburg, I., Selkoe, D.J. (1992) Mutation of the 0-amyloid precursor protein in familial Alzheimer’s disease increases 13-protein production. Nature 360, 672674
Iwatsubo, T., Mann, D.M.A., Odaka, A., Suzuki, N. and Ihara, Y. (1995) Amyloid ß protein (A13) deposition: Aß42(43) precedes A040 in Down syndrome. Ann. Neurol. 37, 294–299.
Lemere, C.A., Blusztajn, J.K., Yamaguchi, H., Wisniewski, T., Saido, T.C. and Selkoe DJ (1996) Sequence of deposition of heterogeneous amyloid 13-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol. Dis. 3, 16–32.
Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.M., Perez-tur, J., Hutton, M., Buee, L., Harigaya, Y., Yager, D., Morgan, D., Gordon, M.N., Holcomb, L., Refolo, L., Zenk, B., Hardy, J., Younkin, S. (1996) Increased amyloid-1342(43) in brains of mice expressing mutant presenilin 1. Nature 383, 710–713.
Tekirian, T.L., Saido, T.C. Markesbery, W.R., Russell, M.J. Wekstein, D.R., Patel, E. and Geddes, J.W. (1998) N-terminal heterogeneity of parenchymal and cerebrovascular Aß deposits. J. Neuropathol. Exp. Neurol. 57, 76–94.
Watson, D., Maat-Schieman, M., Saido, T., Teplow, D., Biere, A.L., Roos, R. and Selkoe, D (1997) N-terminal heterogegeneity of Aß caused by HCHWA-D mutation. Soc. Neurosci. 23, 821 (Abstract 321.9).
Hayashi, Y., Fukatsu, R., Tsuzuki, K., Yoshida, T., Sasaki, N., Kimura, K., Yamaguchi, H., St. George Hyslop, P.H., Fujii, N. and Takahata, N. (1998) Evidence for presenilin-1 involvement in amyloid angiopathy in the Alzheimer’s disease-affected brain. Brain Res. 789, 307–314.
Yamaguchi, H., Ishiguro, K., Sugihara, S., Nakazato, Y., Kawarabayashi, T., Sun, X. and Hirai, S. (1994) Presence of apolipoprotein Eon extracellular neurofibrillary tangles and on meningeal blood vessels precedes the Alzheimer (3-amyloid deposition. Acta Neuropathol. 88, 413–419.
Yamaguchi H and Sugihara S (1997) Aß and its associated proteins with aging: comparison between senile plaques and amyloid angiopathy, in K. Iqbal, B. Winblad, T. Nishimura, M. Takeda M and H.M. Wisniewski (eds.), Alzheimer’s Disease: Biology, Diagnosis and Therapeutics, bon Wiley & Sons, Chichester, pp. 305–309
Vinters, H.V., Natte, R., Maat-Schieman, M.L.C., van Duinen, S.G., Hegeman-Kleinn, I., Welling-Graafland, C., Haan, J. and Roos, R.A.C. (199) Secondary microvaascular degeneration in amyloid angiopathy of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) Acta Neuropathol. 95, 235–244.
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Yamaguchi, H., Maat-Schieman, M.L.C. (2000). Immunohistochemical Analysis of Amyloid β-Protein Isoforms in CAA. 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_10
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DOI: https://doi.org/10.1007/978-94-017-1007-7_10
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