Abstract
Both acquired and familial amyloid neuropathies carry a poor prognosis. In addition, amyloid is sometimes difficult to visualise in nerve biopsy specimens, and the pathogenesis of nerve lesions is still a matter of controversy. In order to learn more on the subject, we studied nerve specimens from seven patients with proven amyloid neuropathy by ultrastructural immunocytochemistry in order to better understand their pathogeny and to evaluate the reliability of the method for detection of amyloid antigens in the endoneurium. An indirect immunolabelling technique using protein A-gold complex (pA-g) was applied. Polyclonal antisera against human IgG, IgM, lambda and kappa light chains and prealbumin were assayed. Amyloid fibrils were labelled in six of seven cases: in four cases with anti-transthyretin (TTR) antibodies and in two with anti-lambda light chain antibodies. The type of immunolabelling correlated with the biochemical type of the amyloidosis as defined by TTR gene analysis and serum immunoelectrophoresis. The amyloid fibrils and gold labelling were always located in the endoneurial space. No intracellular deposit or labelling was found. The immunolabelling was highly specific, gold particles being detected only near to amyloid fibrils with no background gold labelling. Ultrastructural immunolabelling with pA-g could be used for detection of amyloid in progressive axonal neuropathy of unknown origin, with important therapeutic implications.
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References
Adams D, Reilly M, Harding AE, Said G (1992) Mise en évidence de mutation génétique dans la majorité des neuropathies amyloides d'apparence sporadique. Rev Neurol (Paris) 148: 736–741
Coutinho P, Martins da Silva Lopes Lima J, Resende Barbosa A (1980) Forty years of experience with type I amyloid neuropathy. Review of 483 cases. In: Glenner GG, Pinho P, Costa E, Falcao De Freitas A (eds) Amyloid and amyloidosis. Excerpta Medica, Amsterdam, pp 88–98
Donini U, Casanova S, Zucchelli P, Linke RP (1989) Immunoelectron microscopic classification of amyloid in renal biopsies. J Histochem Cytochem 37:1101–1106
Dyck PJ, Lambert EH (1969) Dissociated sensation in amyloidosis. Arch Neurol 20: 490–507
Fujimura H, Lacroix C, Said G (1991) Vulnerability of nerve fibers to ischemia: a quantitative study. Brain 114:1929–1942
Gorevic PD, Rodrigues MM, Spencer WH, Munoz PC, Allen AW, Verne AZ (1987) Prealbumin: a major constituent of vitreous amyloid. Ophthalmology 94:792–798
Haltia M, Prelli F, Ghiso J, et al (1990) Amyloid protein in familial amyloidosis (Finnish type) is homologous to gelsolin, an actin-binding protein. Biochem Biophys Res Commun 167: 927–932
Herrera GA (1992) Ultrastructural immunolabeling: a general overview of techniques and applications. Ultrastruct Pathol 16: 37–45
Holmgren G, Steen L, Ekstedt J, et al (1991) Biochemical effect of liver transplantation in two Swedish patients with familial amyloidotic polyneuropathy (FAP-met30). Clin Genet 40: 242–246
Holt IJ, Harding AE, Middleton L, et al (1989) Molecular genetics of amyloid neuropathy in Europe. Lancet 40:524–526
Kelly JJ, Kyle RA, O'Brien PC, Dyck PJ (1979) The natural history of peripheral neuropathy in primary systemic amyloidosis. Ann Neurol 6: 1–7
Kelly JJ, Kyle RA, Miles JM, O'Brien PC, Dyck PJ (1981) The spectrum of peripheral neuropathy in myeloma. Neurology 31: 24–31
Newman GR, Hobot JA (1987) Modern acrylics for post-embedding immunostaining techniques. J Histochem Cytochem 35: 971
Nichols WC, Dwulet FE, Liepnieks J, Benson MD (1988) Variant apolipoprotein Al as a major constituent of a human hereditary amyloid. Biochem Biophys Res Commun 156: 762–768
Reilly M, King RHM (1993) Familial amyloid polyneuropathy. Brain Pathol 3: 165–176
Reilly M, Adams D, Davis MB, Said G, Harding AE (1995) Haplotype analysis of french, british and other european patients with familial amyloid polyneuropathy. J Neurol 242: 664–668
Said G, Ropert A, Faux N (1984) Length dependent degeneration of fibers in Portuguese amyloid polyneuropathy: a clinicopathologic study. Neurology 34:1025–1032
Saraiva MJM, Birken S, Costa PP, Goodman DS (1984) Amyloid fibril protein in familial amyloidotic polyneuropathy, Portuguese type. J Clin Invest 74: 104–119
Sasaki H, Sakaki Y, Matsuo H, et al (1984) Diagnosis of familial amyloid polyneuropathy by recombinant DNA techniques. Biochem Biophys Res Commun 125: 636–642
Shirahama T, Cohen AS (1967) High resolution electron microscopic analysis of the amyloïd fibril. J Cell Biol 33: 679–708
Sommer C, Schroder JM (1989) Amyloid neuropathy: immunocytochemical localization of intra- and extracellular immunoglobulin light chains. Acta Neuropathol (Berl) 79: 190–199
Stirling JW (1990) Immuno- and affinity probes for electron microscopy: a review of labelling and preparation techniques. J Histochem Cytochem 38: 145–158
Toyoda M, Kita S, Furiya K, Osamura Y (1991) Characterization of AL amyloid protein identified by immunoelectron microscopy: a simple method using the protein A-gold technique. J Histochem Cytochem 39: 239–242
Trotter JL, Engel WK, Ignaczak TF (1977) Amyloidosis with plasma cell dyscrasia: an overlooked cause of adult onset sensorimotor neuropathy. Arch Neurol 34: 209–214
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Adams, D., Said, G. Ultrastructural immunolabelling of amyloid fibrils in acquired and hereditary amyloid neuropathies. J Neurol 243, 63–67 (1996). https://doi.org/10.1007/BF00878533
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DOI: https://doi.org/10.1007/BF00878533