Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1988 Oct;133(1):150–162.

Immunohistochemical study of cerebral amyloid angiopathy. II. Enhancement of immunostaining using formic acid pretreatment of tissue sections.

H V Vinters 1, W M Pardridge 1, D L Secor 1, N Ishii 1
PMCID: PMC1880657  PMID: 3177597

Abstract

Cerebral amyloid angiopathy (CAA) is a biochemically heterogeneous entity most commonly associated with stroke syndromes, Alzheimer's disease (AD), Down's syndrome, and miscellaneous neurologic conditions. The authors have applied and extended (using formic acid pretreatment of histologic sections) an immunocytochemical technique that used antibody to a synthetic 28-amino acid peptide representing a segment of the AD amyloid precursor, to study CAA and related parenchymal amyloid deposits in brain tissues originally derived from: 1) patients with CAA with or without typical clinicopathologic features of AD, cerebral hemorrhage, and infarcts; 2) a young boy with angiocentric brain amyloid; 3) patients with familial (Icelandic, Dutch) forms of cerebral hemorrhage caused by CAA; and 4) Japanese patients with nonfamilial CAA-related brain hemorrhage, sometimes associated with histopathology characteristic of AD. Formic acid pretreatment of sections resulted in markedly enhanced staining of senile plaque core and microvascular, especially capillary, amyloid, and some apparent staining of the neuritic component of senile plaques. Perivascular halos of immunoreactive material were observed frequently. Neurofibrillary tangles were not immunolabeled, nor were blood vessels or any parenchymal components within cerebral white matter. CAA in Japanese patients with nonfamilial encephalic hemorrhages appeared immunocytochemically identical to AD-related CAA. Arterioles in brains that had severe CAA frequently showed significant stenosis of their lumina by nonamyloid hyaline or cellular material.

Full text

PDF
150

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allsop D., Landon M., Kidd M., Lowe J. S., Reynolds G. P., Gardner A. Monoclonal antibodies raised against a subsequence of senile plaque core protein react with plaque cores, plaque periphery and cerebrovascular amyloid in Alzheimer's disease. Neurosci Lett. 1986 Jul 24;68(2):252–256. doi: 10.1016/0304-3940(86)90152-7. [DOI] [PubMed] [Google Scholar]
  2. Allsop D., Landon M., Kidd M. The isolation and amino acid composition of senile plaque core protein. Brain Res. 1983 Jan 24;259(2):348–352. doi: 10.1016/0006-8993(83)91273-8. [DOI] [PubMed] [Google Scholar]
  3. Ball M. J. Alzheimer's disease: a challenging enigma. Arch Pathol Lab Med. 1982 Apr;106(4):157–162. [PubMed] [Google Scholar]
  4. Bergeron C., Ranalli P. J., Miceli P. N. Amyloid angiopathy in Alzheimer's disease. Can J Neurol Sci. 1987 Nov;14(4):564–569. [PubMed] [Google Scholar]
  5. Bobin S. A., Currie J. R., Merz P. A., Miller D. L., Styles J., Walker W. A., Wen G. Y., Wisniewski H. M. The comparative immunoreactivities of brain amyloids in Alzheimer's disease and scrapie. Acta Neuropathol. 1987;74(4):313–323. doi: 10.1007/BF00687207. [DOI] [PubMed] [Google Scholar]
  6. Coria F., Castaño E. M., Frangione B. Brain amyloid in normal aging and cerebral amyloid angiopathy is antigenically related to Alzheimer's disease beta-protein. Am J Pathol. 1987 Dec;129(3):422–428. [PMC free article] [PubMed] [Google Scholar]
  7. Ghiso J., Jensson O., Frangione B. Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C). Proc Natl Acad Sci U S A. 1986 May;83(9):2974–2978. doi: 10.1073/pnas.83.9.2974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gilbert J. J., Vinters H. V. Cerebral amyloid angiopathy: incidence and complications in the aging brain. I. Cerebral hemorrhage. Stroke. 1983 Nov-Dec;14(6):915–923. doi: 10.1161/01.str.14.6.915. [DOI] [PubMed] [Google Scholar]
  9. Glenner G. G., Henry J. H., Fujihara S. Congophilic angiopathy in the pathogenesis of Alzheimer's degeneration. Ann Pathol. 1981;1(2):120–129. [PubMed] [Google Scholar]
  10. Glenner G. G. On causative theories in Alzheimer's disease. Hum Pathol. 1985 May;16(5):433–435. doi: 10.1016/s0046-8177(85)80078-2. [DOI] [PubMed] [Google Scholar]
  11. Glenner G. G., Wong C. W. Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1131–1135. doi: 10.1016/0006-291x(84)91209-9. [DOI] [PubMed] [Google Scholar]
  12. Glenner G. G., Wong C. W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984 May 16;120(3):885–890. doi: 10.1016/s0006-291x(84)80190-4. [DOI] [PubMed] [Google Scholar]
  13. Goldgaber D., Lerman M. I., McBride O. W., Saffiotti U., Gajdusek D. C. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science. 1987 Feb 20;235(4791):877–880. doi: 10.1126/science.3810169. [DOI] [PubMed] [Google Scholar]
  14. Gross P. M., Sposito N. M., Pettersen S. E., Fenstermacher J. D. Differences in function and structure of the capillary endothelium in gray matter, white matter and a circumventricular organ of rat brain. Blood Vessels. 1986;23(6):261–270. doi: 10.1159/000158652. [DOI] [PubMed] [Google Scholar]
  15. Gudmundsson G., Hallgrímsson J., Jónasson T. A., Bjarnason O. Hereditary cerebral haemorrhage with amyloidosis. Brain. 1972;95(2):387–404. doi: 10.1093/brain/95.2.387. [DOI] [PubMed] [Google Scholar]
  16. Guiroy D. C., Miyazaki M., Multhaup G., Fischer P., Garruto R. M., Beyreuther K., Masters C. L., Simms G., Gibbs C. J., Jr, Gajdusek D. C. Amyloid of neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2073–2077. doi: 10.1073/pnas.84.7.2073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ishii N., Nishihara Y., Horie A. Amyloid angiopathy and lobar cerebral haemorrhage. J Neurol Neurosurg Psychiatry. 1984 Nov;47(11):1203–1210. doi: 10.1136/jnnp.47.11.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kang J., Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Multhaup G., Beyreuther K., Müller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987 Feb 19;325(6106):733–736. doi: 10.1038/325733a0. [DOI] [PubMed] [Google Scholar]
  19. Katzman R. Alzheimer's disease. N Engl J Med. 1986 Apr 10;314(15):964–973. doi: 10.1056/NEJM198604103141506. [DOI] [PubMed] [Google Scholar]
  20. Kitamoto T., Ogomori K., Tateishi J., Prusiner S. B. Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids. Lab Invest. 1987 Aug;57(2):230–236. [PubMed] [Google Scholar]
  21. Löfberg H., Grubb A. O., Nilsson E. K., Jensson O., Gudmundsson G., Blöndal H., Arnason A., Thorsteinsson L. Immunohistochemical characterization of the amyloid deposits and quantitation of pertinent cerebrospinal fluid proteins in hereditary cerebral hemorrhage with amyloidosis. Stroke. 1987 Mar-Apr;18(2):431–440. doi: 10.1161/01.str.18.2.431. [DOI] [PubMed] [Google Scholar]
  22. Mandybur T. I. The incidence of cerebral amyloid angiopathy in Alzheimer's disease. Neurology. 1975 Feb;25(2):120–126. doi: 10.1212/wnl.25.2.120. [DOI] [PubMed] [Google Scholar]
  23. Masters C. L., Multhaup G., Simms G., Pottgiesser J., Martins R. N., Beyreuther K. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J. 1985 Nov;4(11):2757–2763. doi: 10.1002/j.1460-2075.1985.tb04000.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Masters C. L., Simms G., Weinman N. A., Multhaup G., McDonald B. L., Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245–4249. doi: 10.1073/pnas.82.12.4245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Miyakawa T., Shimoji A., Kuramoto R., Higuchi Y. The relationship between senile plaques and cerebral blood vessels in Alzheimer's disease and senile dementia. Morphological mechanism of senile plaque production. Virchows Arch B Cell Pathol Incl Mol Pathol. 1982 Aug;40(2):121–129. doi: 10.1007/BF02932857. [DOI] [PubMed] [Google Scholar]
  26. Miyakawa T., Uehara Y. Observations of amyloid angiopathy and senile plaques by the scanning electron microscope. Acta Neuropathol. 1979 Nov;48(2):153–156. doi: 10.1007/BF00691158. [DOI] [PubMed] [Google Scholar]
  27. Ogata J., Okayama M., Goto I., Inomata H., Yoshida I., Omae T. Primary familial amyloidosis with vitreous opacities. Report of an autopsy case. Acta Neuropathol. 1978 Apr 26;42(1):67–70. doi: 10.1007/BF01273271. [DOI] [PubMed] [Google Scholar]
  28. Okayama M., Goto I., Ogata J., Omae T., Yoshida I., Inomata H. Primary amyloidosis with familial vitreous opacities: an unusual case and family. Arch Intern Med. 1978 Jan;138(1):105–111. [PubMed] [Google Scholar]
  29. Okazaki H., Reagan T. J., Campbell R. J. Clinicopathologic studies of primary cerebral amyloid angiopathy. Mayo Clin Proc. 1979 Jan;54(1):22–31. [PubMed] [Google Scholar]
  30. Pardridge W. M., Vinters H. V., Miller B. L., Tourtellotte W. W., Eisenberg J. B., Yang J. High molecular weight Alzheimer's disease amyloid peptide immunoreactivity in human serum and CSF is an immunoglobulin G. Biochem Biophys Res Commun. 1987 May 29;145(1):241–248. doi: 10.1016/0006-291x(87)91312-x. [DOI] [PubMed] [Google Scholar]
  31. Pardridge W. M., Vinters H. V., Yang J., Eisenberg J., Choi T. B., Tourtellotte W. W., Huebner V., Shively J. E. Amyloid angiopathy of Alzheimer's disease: amino acid composition and partial sequence of a 4,200-dalton peptide isolated from cortical microvessels. J Neurochem. 1987 Nov;49(5):1394–1401. doi: 10.1111/j.1471-4159.1987.tb01005.x. [DOI] [PubMed] [Google Scholar]
  32. Price D. L. New perspectives on Alzheimer's disease. Annu Rev Neurosci. 1986;9:489–512. doi: 10.1146/annurev.ne.09.030186.002421. [DOI] [PubMed] [Google Scholar]
  33. Robakis N. K., Ramakrishna N., Wolfe G., Wisniewski H. M. Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4190–4194. doi: 10.1073/pnas.84.12.4190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Selkoe D. J. Altered structural proteins in plaques and tangles: what do they tell us about the biology of Alzheimer's disease? Neurobiol Aging. 1986 Nov-Dec;7(6):425–432. doi: 10.1016/0197-4580(86)90055-2. [DOI] [PubMed] [Google Scholar]
  35. Selkoe D. J., Bell D. S., Podlisny M. B., Price D. L., Cork L. C. Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease. Science. 1987 Feb 20;235(4791):873–877. doi: 10.1126/science.3544219. [DOI] [PubMed] [Google Scholar]
  36. Shaw C. M. Primary idiopathic cerebrovascular amyloidosis in a child. Brain. 1979 Mar;102(1):177–192. doi: 10.1093/brain/102.1.177. [DOI] [PubMed] [Google Scholar]
  37. Snow A. D., Willmer J. P., Kisilevsky R. Sulfated glycosaminoglycans in Alzheimer's disease. Hum Pathol. 1987 May;18(5):506–510. doi: 10.1016/s0046-8177(87)80036-9. [DOI] [PubMed] [Google Scholar]
  38. Stewart P. A., Magliocco M., Hayakawa K., Farrell C. L., Del Maestro R. F., Girvin J., Kaufmann J. C., Vinters H. V., Gilbert J. A quantitative analysis of blood-brain barrier ultrastructure in the aging human. Microvasc Res. 1987 Mar;33(2):270–282. doi: 10.1016/0026-2862(87)90022-7. [DOI] [PubMed] [Google Scholar]
  39. Tanzi R. E., Gusella J. F., Watkins P. C., Bruns G. A., St George-Hyslop P., Van Keuren M. L., Patterson D., Pagan S., Kurnit D. M., Neve R. L. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science. 1987 Feb 20;235(4791):880–884. doi: 10.1126/science.2949367. [DOI] [PubMed] [Google Scholar]
  40. Tanzi R. E., St George-Hyslop P. H., Haines J. L., Polinsky R. J., Nee L., Foncin J. F., Neve R. L., McClatchey A. I., Conneally P. M., Gusella J. F. The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid beta-protein gene. Nature. 1987 Sep 10;329(6135):156–157. doi: 10.1038/329156a0. [DOI] [PubMed] [Google Scholar]
  41. Vinters H. V. Cerebral amyloid angiopathy. A critical review. Stroke. 1987 Mar-Apr;18(2):311–324. doi: 10.1161/01.str.18.2.311. [DOI] [PubMed] [Google Scholar]
  42. Vinters H. V., Gilbert J. J. Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke. 1983 Nov-Dec;14(6):924–928. doi: 10.1161/01.str.14.6.924. [DOI] [PubMed] [Google Scholar]
  43. Vinters H. V., Miller B. L., Pardridge W. M. Brain amyloid and Alzheimer disease. Ann Intern Med. 1988 Jul 1;109(1):41–54. doi: 10.7326/0003-4819-109-1-41. [DOI] [PubMed] [Google Scholar]
  44. Vinters H. V., Pardridge W. M., Yang J. Immunohistochemical study of cerebral amyloid angiopathy: use of an antiserum to a synthetic 28-amino-acid peptide fragment of the Alzheimer's disease amyloid precursor. Hum Pathol. 1988 Feb;19(2):214–222. doi: 10.1016/s0046-8177(88)80352-6. [DOI] [PubMed] [Google Scholar]
  45. Vinters H. V., Reave S., Costello P., Girvin J. P., Moore S. A. Isolation and culture of cells derived from human cerebral microvessels. Cell Tissue Res. 1987 Sep;249(3):657–667. doi: 10.1007/BF00217338. [DOI] [PubMed] [Google Scholar]
  46. Wong C. W., Quaranta V., Glenner G. G. Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8729–8732. doi: 10.1073/pnas.82.24.8729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wurtman R. J. Alzheimer's disease. Sci Am. 1985 Jan;252(1):62-6, 71-4. doi: 10.1038/scientificamerican0185-62. [DOI] [PubMed] [Google Scholar]
  48. van Duinen S. G., Castaño E. M., Prelli F., Bots G. T., Luyendijk W., Frangione B. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5991–5994. doi: 10.1073/pnas.84.16.5991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES