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Hereditary cerebral hemorrhage with amyloidosis (Dutch): a model for congophilic plaque formation without neurofibrillary pathology

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Abstract

Plaque-like lesions and amyloid angiopathy were investigated in the frontal cerebral cortex of four patients with hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D), using immunohistochemical [antibodies to β amyloid protein (Aβ), β protein precursor (βPP), synaptophysin, ubiquitin (UBQ), cathepsin D, paired helical filaments (PHF) and glial fibrillary acidic protein (GFAP)], enzymehistochemical (acid phosphatase) and silver [methenamine silver (MS) and Palmgren] staining methods. Whereas Aβ-and MS-positive diffuse plaques were found in all patients, only the three older patients showed neuritic or congophilic plaques, which were acid phosphatase and cathepsin D positive and contained βPP-, synaptophysin-and UBQ-positive, but PHF-negative neurites. These plaques were surrounded by reactive astrocytes. Similar immuno-and enzymereactivity was found around congophilic blood vessels. Thus, apart from neuronal degeneration in a subset of plaque-like lesions and around blood vessels, this study shows an age-related morphology of the plaques in HCHWA-D, corresponding to that in Down's syndrome (DS), with the difference that neurofibrillary (NF) pathology is absent in HCHWA-D in contrast to DS. HCHWA-D may be considered as a model for congophilic plaque formation not associated with NF pathology.

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References

  1. Arai H, Lee VM-Y, Otvos L, Greenberg BD, Lowery DE, Sharma SK, Schmidt ML, Trojanowski JQ (1990) Defined neurofilament, τ, and β-amyloid precursor protein epitopes distinguish Alzheimer from non-Alzheimer senile plaques. Proc Natl Sci USA 87: 2249–2253

    Google Scholar 

  2. Bakker E, van Broekhoven C, Haan J, Voorhoeve E, van Hul W, Levy E, Lieberburg I, Carman MD, van Ommen GJB, Frangione B, Roos RAC (1991) DNA diagnosis for hereditary cerebral hemorrhage with amyloidosis (Dutch type). Am J Hum Genet 49: 518–521

    Google Scholar 

  3. Barka T (1960) A simple azo-dye method for histochemical demonstration of acid phosphatase. Nature 187: 284–289

    Google Scholar 

  4. Benowitz LI, Rodriguez W, Paskevich P, Mufson EJ, Schenk D, Neve RL (1989) The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects. Exp Neurol 106: 237–250

    Google Scholar 

  5. Brion J-P, Couck A-M, Bruce M, Anderton B, Flament-Durand J (1991) Synaptophysin and chromogranin A immunoreactivities in senile plaques of Alzheimer's disease. Brain Res 539: 143–150

    Google Scholar 

  6. Cataldo AM, Thayer CY, Bird ED, Wheelock TR, Nixon RA (1990) Lysosomal proteinase antigens are prominantly localized within senile plaques of Alzheimer's disease: evidence for a neuronal origin. Brain Res 513: 181–192

    Google Scholar 

  7. Cataldo AM, Paskevich PA, Kominami E, Nixon RA (1991) Lysosomal hydrolases of different classes are abnormally distributed in brains of patients with Alzheimer disease. Proc Natl Acad Sci USA 88: 10998–11002

    Google Scholar 

  8. Cochran E, Bacci B, Chen Y, Patton A, Gambetti P, Autilio-Gambetti L (1991) Amyloid precursor protein and ubiquitin immunoreactivity in dystrophic axons is not unique to Alzheimer's disease. Am J Pathol 139: 485–489

    Google Scholar 

  9. Cole GM, Masliah E, Shelton ER, Chan HW, Terry RD, Saitoh T (1991) Accumulation of amyloid precursor fragment in Alzheimer plaques. Neurobiol Aging 12: 85–92

    Google Scholar 

  10. Cras P, Kawai M, Lowery D, Gonzales-DeWhitt P, Greenberg B, Perry G (1991) Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein. Proc Natl Acad Sci USA 88: 7552–7556

    Google Scholar 

  11. Cummings BJ, Su JH, Geddes JW, Van Nostrand WE, Wagner SL, Cunningham DD, Cotman CW (1992) Aggregation of the amyloid precursor protein within degenerating neurons and dystrophic neurites in Alzheimer's disease. Neuroscience 48: 763–777

    Google Scholar 

  12. Dickson DW, Wertkin A, Mattiace LA, Fier E, Kress Y, Davies P, Yen S-H (1990) Ubiquitin immunoelectron microscopy of dystrophic neurites in cerebellar senile plaques of Alzheimer's disease. Acta Neuropathol 79: 486–493

    Google Scholar 

  13. Duinen SG van, Castaõ EM, Prelli F, Bots GTAM, Luyendijk W, Frangione B (1987) Hereditary cerebral hemorrhage with amyloidosis of Dutch origin is related to Alzheimer's disease. Proc Natl Acad Sci USA 84: 5991–5994

    Google Scholar 

  14. Fraser PE, Nguyen JT, Inouye H, Surewicz WK, Selkoe DJ, Podlisny MB, Kirschner DA (1992) Fibril formation by primate, rodent, and Dutch-hemorrhagic analogues of Alzheimer amyloid β-protein. Biochemistry 31: 10716–10723

    Google Scholar 

  15. Giaccone G, Tagliavini F, Linoli G, Bouras C, Frigerio L, Frangione B, Bugiani O (1989) Down patients: extracellular preamyloid deposits precede neuritic degeneration and senile plaques. Neurosci Lett 97: 232–238

    Google Scholar 

  16. Haan J, Roos RAC, Briët P, Herpers MJHM, Luyendijk W, Bots GTAM (1989) Hereditary cerebral hemorrhage with amyloidosis-Dutch type: clinical characteristics. Clin Neurol Neurosurg 81: 285–290

    Google Scholar 

  17. Haan J, Bakker E, Jennekens-Schinkel A, Roos RAC (1992) Progressive dementia, without cerebral hemorrhage, in a patient with hereditary cerebral amyloid angiopathy. Clin Neurol Neurosurg 94: 317–318

    Google Scholar 

  18. Haass C, Koo EH, Mellon A, Hung AY, Selkoe DJ (1992) Targeting of cell-surface β-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments. Nature 357: 500–503

    Google Scholar 

  19. Hyman BT, Tanzi RE, Marzloff K, Barbour R, Schenk D (1992) Kunitz protease inhibitor-containing amyloid β protein precursor immunoreactivity in Alzheimer's disease. J Neuropathol Exp Neurol 51: 76–83

    Google Scholar 

  20. Ihara Y, Abraham C, Selkoe D (1983) Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins. Nature 304: 727–730

    Google Scholar 

  21. Ishii T, Kametani F, Haga S, Sato M (1989) The immunohistochemical demonstration of subsequences of the precursor of the amyloid A4 protein in senile plaques in Alzheimer's disease. Neuropathol Appl Neurobiol 15: 135–147

    Google Scholar 

  22. Joachim CL, Mori H, Selkoe DJ (1989) Amyloid beta-protein in tissues other than brain in Alzheimer's disease. Nature 341: 226–230

    Google Scholar 

  23. Joachim C, Games D, Morris J, Ward P, Frenkel D, Selkoe D (1991) Antibodies to non-beta regions of the beta-amyloid precursor protein detect a subset of senile plaques. Am J Pathol 138: 373–384

    Google Scholar 

  24. Kametani F, Tanaka K, Ishii T, Ikeda S, Kennedy HE, Allsop D (1993) Secretory form of Alzheimer amyloid precursor protein 695 in human brain lacks β/A4 amyloid immunoreactivity. Biochem Biophys Res Commun 191: 392–398

    Google Scholar 

  25. Kawai M, Cras P, Richey P, Tabaton M, Lowery DE, Gonzales-DeWhitt PA, Greenberg BD, Gambetti P, Perry G (1992) Subcellular localization of amyloid precursor protein in senile plaques of Alzheimer's disease. Am J Pathol 140: 947–958

    Google Scholar 

  26. Levy E, Carman MD, Fernandez-Madrid IJ, Power MD, Lieberburg I, van Duinen SG, Bots GTAM, Luyendijk W, Frangione B (1990) Mutation of Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science 248: 1124–1126

    Google Scholar 

  27. Maat-Schieman MLC, van Duinen SG, Haan J, Roos RAC (1992) Morphology of cerebral plaque-like lesions in hereditary cerebral hemorrhage with amyloidosis (Dutch). Acta Neuropathol 84: 674–679

    Google Scholar 

  28. Mann DMA, Brown A, Prinja D, Davies CA, Landon M, Masters CL, Beyreuther K (1989) An analysis of the morphology of senile plaques in Down's syndrome patients of different ages using immunocytochemical and lectin histochemical techniques. Neuropathol Appl Neurobiol 15: 317–329

    Google Scholar 

  29. Masliah E, Hansen L, Albright T, Mallory M, Terry RD (1991) Immunoelectron microscopic study of synaptic pathology in Alzheimer's disease. Acta Neuropathol 81: 428–433

    Google Scholar 

  30. Mattiace LA, Kress Y, Davies P, Ksiezak-Reding H, Yen S-H, Dickson DW (1991) Ubiquitin-immunoreactive dystrophic neurites in Down's syndrome brain. J Neuropathol Exp Neurobiol 5: 547–559

    Google Scholar 

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

    Google Scholar 

  32. Oghami T, Kitamoto T, Weidmann A, Beyrether K, Tateishi J (1991) Alzheimer's amyloid precursor protein-positive degenerative neurites exist even within Kuru plaques not specific to Alzheimer's disease. Am J. Pathol 139: 1245–1250

    Google Scholar 

  33. Ohgami T, Kitamoto T, Tateishi J (1992) Alzheimer's amyloid precursor protein accumulates within axonal swellings in human brain lesions. Neurosci Lett 136: 75–78

    Google Scholar 

  34. Perry G, Lipphardt S, Mulvihill P, Kancherla M, Mijares M, Gambetti P, Sharma S, Maggiora L, Cornette J, Lobl T, Greenberg B (1988) Amyloid precursor protein in senile plaques of Alzheimer disease. Lancet II: 746

    Google Scholar 

  35. Probst A, Anderton BH, Brion J-P, Ulrich J (1989) Senile plaque neurites fail to demonstrate anti-paried helical filament and anti-microtubule-associated protein-tau immunoreactive proteins in the absence of neurofibrillary tangles in the neocortex. Acta Neuropathol 77: 430–436

    Google Scholar 

  36. Rozemuller AJM, Eikelenboom P, Stam FC, Beyreuther K, Masters CL (1989) A4 Protein in Alzheimer's disease: primary and secondary cellular events in extracellular amyloid deposition. J Neuropathol Exp Neurol 48: 674–691

    Google Scholar 

  37. Rozemuller AJM, Roos RAC, Bots GTAM, Kamphorst W, Eikelenboom P, Van Nostrand WE (1993) Distribution of β/A4 protein and amyloid precursor protein in hereditary cerebral hemorrhage with amyloidosis-Dutch type and Alzheimer's disease. Am J Pathol 142: 1449–1457

    Google Scholar 

  38. Shoji M, Hirai S, Yamaguchi H, Harigaya Y, Kawarabayashi T (1990) Amyloid β-protein precursor accumulates in dystrophic neurites of senile plaques in Alzheimer-type dementia. Brain Res 512: 164–168

    Google Scholar 

  39. Shoji M, Golde TE, Ghiso J, Cheung TT, Estus S, Shaffer LM, Cai Y-D, McKay 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 

  40. Suzuki K, Terry RD (1967) Fine structural localization of acid phosphatase in senile plaques in Alzheimer's presenile dementia. Acta Neuropathol (Berl) 8: 276–284

    Google Scholar 

  41. Tabaton M, Cammarata S, Mandybur T, Richey P, Kawai M, Perry G, Gambetti P (1992) Senile plaques in cerebral amyloid angiopathy show accumulation of amyloid precursor protein without cytoskeletal abnormalities. Brain Res 593: 299–303

    Google Scholar 

  42. Tagliavini F, Giaccone G, Frangione B, Bugiani O (1988) Preamyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals. Neurosci Lett 93: 191–196

    Google Scholar 

  43. Tagliavini F, Giaccone G, Bugiani O, Frangione B (1993) Ubiquitinated neurites are associated with preamyloid and cerebral amyloid β deposits in patients with hereditary cerebral hemorrhage with amyloidosis Dutch type. Acta Neuropathol 85: 267–271

    Google Scholar 

  44. Van Nostrand WE, Wagner SL, Suzuki M, Choi BH, Farrow JS, Geddes JW, Cotman CW, Cunningham DD (1989) Protease nexin-2, a potent anti-chymotrypsin, shows identity to amyloid β-protein precursor. Nature 341: 546–549

    Google Scholar 

  45. Wasco W, Bupp K, Magendantz K, Gusella JF, Tanzi RE, Solomon F (1992) Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid β protein precursor. Proc Natl Acad Sci USA 89: 10758–10762

    Google Scholar 

  46. Wasco W, Brook JD, Tanzi RE (1993) The amyloid precursor-like protein (APLP) gene maps to the long arm of human chromosome 19. Genomics 15: 237–239

    Google Scholar 

  47. Wisniewski HM, Terry RD (1973) Reexamination of the pathogenesis of the senile plaque. Neuropathol 2: 1–26

    Google Scholar 

  48. Yamaguchi H, Nakazato Y, Hirai S, Shoji M, Harigaya Y (1989) Electron micrograph of diffuse plaques. Initial stage of senile plaque formation in the Alzheimer brain. Am J Pathol 135: 593–597

    Google Scholar 

  49. Yamaguchi H, Hage C, Hirai S, Nakazoto Y, Kosaka S (1990) Distinctive, rapid and easy labeling of diffuse plaques in the Alzheimer brains by a new methenamine silver stain. Acta Neuropathol 79: 569–572

    Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, University Hospital, PO Box 9600, NL-2300 RC, Leiden, The Netherlands

    M. L. C. Maat-Schieman, C. M. Radder, J. Haan & R. A. C. Roos

  2. Department of Pathology, University Hospital, Leiden, The Netherlands

    S. G. van Duinen

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  1. M. L. C. Maat-Schieman
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  3. J. Haan
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  4. R. A. C. Roos
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  5. S. G. van Duinen
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Maat-Schieman, M.L.C., Radder, C.M., Haan, J. et al. Hereditary cerebral hemorrhage with amyloidosis (Dutch): a model for congophilic plaque formation without neurofibrillary pathology. Acta Neuropathol 88, 371–378 (1994). https://doi.org/10.1007/BF00310382

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  • DOI: https://doi.org/10.1007/BF00310382

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