Skip to main content
Log in

Cerebral β amyloid deposition in patients with malignant neoplasms: its prevalence with aging and effects of radiation therapy on vascular amyloid

  • Regular Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

We examined immunohistochemically 123 autopsy brains from patients aged between 30 to 59, who died as a result of malignant neoplasms. Using antiserum to amyloid β protein (Aβ), we found that cerebral Aβ deposits began in the subjects' fifth decade; its prevalence was 0%, 9.8% and 21.5% in the fourth, fifth and sixth decades, respectively. The major form of Aβ deposition was diffuse-type plaques, although one third of the brains with Aβ deposition showed amyloid angiopathy. Subpial Aβ deposition is frequently associated with amyloid angiopathy. The prevalence of cerebral Aβ deposits was about two times higher in the patients who had received brain radiation therapy (27.8%) compared to non-radiated patients (14.8%). Amyloid angiopathy was much more prominent (P<0.05) with radiation therapy (22.2%) than without (8.0%). We found that cerebral Aβ deposition is dependent on aging, even in patients with malignant tumors and at beginning in their forties, and that brain radiation therapy is a possible risk factor of Aβ deposition, especially in the form of amyloid angiopathy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Busciglio J, Gabuzda DH, Matsudaira P, Yankner BA (1993) Generation of β-amyloid in the secretory pathway in neuronal and nonneuronal cells. Proc Natl Acad Sci USA 90:2092–2096

    Google Scholar 

  2. Chartier-Harlin MC, Crowford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Poques P, Hardy J, Mullan M (1991) Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene. Nature 353:844–846

    Google Scholar 

  3. Corder EH, Sanders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pricak-Vance MA (1993) Gene dose of apoprotein E type 4 allele and risk of Alzheimer's disease in late onset families. Science 261:921–923

    Google Scholar 

  4. Davies L, Wolska B, Hilbich C, Multhaup G, Martins R, Simms G, Beyreuther K, Masters CL (1988) A4 amyloid protein deposition and the diagnosis of Alzheimer's disease. Neurology 38:1688–1698

    Google Scholar 

  5. Davis RL, Robertson DM (1991) Cerebral amyloid angiopathy. In: Textbook of Neuropathology, 2nd edn. Williams and Wilkins, Baltimore, p 648

    Google Scholar 

  6. Dayan A (1970) Quantitative histologic studies on the aged human brain. II. Senile plaques and neurofibrillary tangles in senile dementia (with an appendix on their occurrence in cases of carcinoma). Acta Neuropathol (Berl) 16:95–102

    Google Scholar 

  7. Delaere P, He Y, Fayet G, Duyckaerts C, Hauw JJ (1993) Beta A4 deposits are constant in the brain of the oldest old: an immunocytochemical study of 20 French centenarians. Neurobiol Aging 14:191–194

    Google Scholar 

  8. Duchen LW (1992) Effect of X-ray irradiation on the nervous system. In: Adams JH, Duchen LW (eds) Greenfield's neuropathology, 5th edn. Oxford University Press, New York, pp 54–57

    Google Scholar 

  9. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Findani L, Giuffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Roque P, Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349: 704–706

    Google Scholar 

  10. Haass C, Schlossmacher M, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BC, Lieberburg I, Koo EH, Schenk D, Teplow DB, Selkoe DJ (1992) Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 359:322–325

    Google Scholar 

  11. Ihara Y, Kondo J, Miura R, Nakazawa Y, Mori H, Honda T (1990) Characterization of antisera to paired helical filaments and tau. An implication for the extent of tau tightly bound to paired helical filaments. Gerontology 36 [Suppl 1]:15–24

    Google Scholar 

  12. Itoh Y, Yamada M, Hayakawa M, Otomo E Miyatake T (1993) Subpial β/A4 peptide deposits are closely associated with amyloid angiopathy in the elderly. Neurosci Lett 155:144–147

    Google Scholar 

  13. Kang J, Lamaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Muller-Hill B (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733–736

    Google Scholar 

  14. Lampert PW (1968) Amyloid and amyloid like deposits. In: Minckler J (ed) Pathology of the nervous system, vol 1. McGraw-Hill, New York, pp 1113–1121

    Google Scholar 

  15. Mackenzie IRA (1994) Senile plaques do not progressively accumulate with normal aging. Acta Neuropathol 87:520–525

    Google Scholar 

  16. Mann DMA, Esiri MM (1989) The pattern of acquisition of plaques and tangles in the brains of the patients under 50 years of age with Down's syndrome. J Neurol Sci 89:169–179

    Google Scholar 

  17. Mann DMA, Jones D (1990) Deposition of amyloid (A4) protein within the brains of persons with dementing disorders other than Alzheimer's disease and Down's syndrome. Neurosci Lett 109:68–75

    Google Scholar 

  18. Mann DMA, Brown AM, Prinja D, Jones D, Davies CA (1990) A morphological analysis of senile plaques in the brains of non-demented persons of different ages using silver, immunocytochemical and Jectin histochemical staining techniques. Neuropathol Appl Neurobiol 16:17–25

    Google Scholar 

  19. Mann DMA, Jones D, Snowden JS, Neary D, Hardy J (1992) Pathological changes in the brain of the pateint with familial Alzheimer's disease having missense mutation at codon 717 in the amyloid precursor protein gene. Neurosci Lett 137:225–228

    Google Scholar 

  20. Motte J, Williams RS (1989) Age related changes in the density and morphology of plaques and neurofibrillary tangles in Down's syndrome brain. Acta Neuropathol 77:535–546

    Google Scholar 

  21. Murrell J, Farlow M, Ghetti B, Benson MD (1991) A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 254:97–99

    Google Scholar 

  22. Neubürger K, Röusch A (1935) Über argentaphile Ablagerungen im Gehim bei Krebskranken. Virchows Arch 294:537–558

    Google Scholar 

  23. Ogomori K, Kitamoto T, Tateishi J, Sato Y, Tashima T (1988) Aging and cerebral amyloid: early detection of amyloid in the human brain using biochemical extraction and immunostain. J Gerontrol 43:157–162

    Google Scholar 

  24. Roberts GW, Allsop D, Brunton C (1990) The occult aftermath of boxing. J Neurol Neurosurg Psychiatry 53:373–378

    Google Scholar 

  25. Roberts GW, Gentleman SM, Lynch A, Graham DI (1991) βA4 amyloid protein in brain after head trauma. Lancet 338: 1422–1423

    Google Scholar 

  26. Roher AE, Lowenson JD, Clark S, Wolkow C, Wang R, Cotter RJ, Reardon IM, Zurcher-Neely HA, Heinrikson RL, Ball MJ, Greenberg BD (1993) Structural alterations in the peptides backbone of β-amyloid core protein may account for its deposition and stability in Alzheimer's disease. J Biol Chem 268:3072–3083

    Google Scholar 

  27. Sanders AM, Strittmatter WJ, Schmechel D, St. George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-MacLachlan DR, Alberts MJ, Hulette C Crain B, Goldgaber D, Roses AD (1993) Association of apolipoprotein E allele ε4 with late-onset familial and sporadic Alzheimer's disease. Neurology 43:1467–1472

    Google Scholar 

  28. Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Devey H, David D, Shinha S, Schlossmacher M, Whaley J, Swindlehurst C, McCormack R, Wolfert R, Selkoe D, LIeberburg I, Schenk D (1992) Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature 359:325–327

    Google Scholar 

  29. Shoji M, Golde TE, Ghiso J, Cheung TT, Estus S, Shaffer LM, Cai XD, Mackay DM, Tintner R, Frangione B, Younkin SG (1992) Production of the Alzheimer amyloid β protein by normal proteolytic processing. Science 258:126–129

    Google Scholar 

  30. Tokuda T, Ikeda S, Yanagisawa N, Ihara Y, Glenner GG (1991) Re-examination of ex-boxers' brains using immunohistochemistry with antibodies to amyloid β-protein and tau protein. Acta Neuropathol 82:280–285

    Google Scholar 

  31. Tomlinson B, Blessed G (1968) Observations on the brains of non-demented old people. J Neurol Sci 7:331–356

    Google Scholar 

  32. Urlich J (1985) Alzheimer's changes in non-demented patients younger than sixty-five: possible early stages of Alzheimer's disease and senile dementia of Alzheimer type Ann Neurol 17: 273–277

    Google Scholar 

  33. Wisniewski HM, Bancher C, Barcikowska M, Wen GY, Currie J (1989) Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease. Acta Neuropathol 78:337–347

    Google Scholar 

  34. Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Ihara Y (1988) A variety of cerebral amyloid deposits in the brains of Alzheimer-type dementia demonstrated by β protein immunostaining. Acta Neuropathol 76:541–549

    Google Scholar 

  35. Yamaguchi H, Hirai S, Morimatsu M, Harigaya Y (1988) Diffuse type of senile plaques in, the brains of Alzheimer-type dementia. Acta Neuropathol 77:113–119

    Google Scholar 

  36. Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Nakazato Y (1989) Diffuse type of senile plaques in the cerebellum of Alzheimer-type dementia demonstrated by β protein immunostaining. Acta Neuropathol 77:314–319

    Google Scholar 

  37. Yamaguchi H, Yamazaki T, Lemere CL, Frosch MP, Selkoe DJ (1992) Beta amyloid is focally depoited within the outer basement membrane in the amyloid angiopathy of Alzheimer's disease: an immunoelectron microscopic study. Am J Pathol 141:249–259

    Google Scholar 

  38. Yamaguchi H, Ishiguro K, Sugihara S, Nakazato Y, Kawarabayashi T, Sun X, Hirai S (1994) Presence of apolipoprotein E on extracellular neurofibrillary tangles and on meningeal blood vessels precedes the Alzheimer β-amyloid deposition. Acta Neuropathol 88:413–419

    Google Scholar 

  39. Yamashita J (1937) Neuropathological findings of the patients with carcinomas (in Japanese). Fukuoka Med J 31:575–632

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugihara, S., Ogawa, A., Nakazato, Y. et al. Cerebral β amyloid deposition in patients with malignant neoplasms: its prevalence with aging and effects of radiation therapy on vascular amyloid. Acta Neuropathol 90, 135–141 (1995). https://doi.org/10.1007/BF00294312

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00294312

Key words

Navigation