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Migration of perivascular cells into the neuropil and their involvement in β-amyloid plaque formation

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Summary

Our recent ultrastructural studies of amyloid angiopathy in biopsy specimens from Alzheimer's disease patients showed that perivascular cells and perivascular microglia are involved in the production of amyloid fibrils. Further examination of the walls of the vessels with and without amyloid deposits presented in this report reveals numerous mononuclear cells with a broad spectrum of morphological appearances. Some of these cells produce amyloid in the vascular wall and migrate into the neuropil. Others do not produce amyloid in this location but also migrate through the vascular basal lamina and position themselves on the external surface of basal lamina or in the neuropil outside the vascular astrocytic end-feet processes. The presence of clusters or rows of six or more of these cells in the position of perivascular microglial cells suggests their proliferation in the perivascular region. After leaving the perimeter of the vessel wall, perivascular cells become the perivascular, neuropil, and satellite microglia cells. Migrating perivascular cells become the microglia, which are engaged in amyloid fibril formation and development of classical and primitive plaques.

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References

  1. Boya J, Calvo J, Prado A (1979) The origin of microglial cells. J Anat 129:177–186

    Google Scholar 

  2. Brierly JB, Brown AW (1982) The origin of lipid phagocytes in the central nervous system. I. The intrinsic microglia. J Comp Neurol 211:397–406

    Google Scholar 

  3. Cork LC, Masters C, Beyreuther K, Price DL (1990) Development of senile plaques. Relationships of neuronal abnormalities and amyloid deposits. Am J Pathol 137:1383–1392

    Google Scholar 

  4. Giulian D, Baker TJ (1986) Characterization of ameboid microglia isolated from developing mammalian brain. J Neurosci 6:2163–2178

    Google Scholar 

  5. Goate A, Chartier-Harlin M-C, Mullan M, Brown J, Crawford F, Fidani L, Giufra A, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Roques 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 

  6. Graeber MB, Streit WJ (1990) Perivascular microglia defined. Trends Neurosci 13:66

    Google Scholar 

  7. Graeber MB, Streit WJ, Kreutzberg GW (1989) Identity of ED2-positive perivascular cells in rat brain. J Neurosci Res 22:103–106

    Google Scholar 

  8. Graeber MB, Streit WJ, Buringer D, Sparks DL, Kreutzberg GW (1992) Ultrastructural location of major histocompatibility complex (MHC) class II-positive perivascular cells in histologically normal human brain. J Neuropathol Exp Neurol 51:303–311

    Google Scholar 

  9. Hickey WF, Kimura H (1988) Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239:290–292

    Google Scholar 

  10. Hickey WF, Vass K, Lassman H (1992) Bone marrow-derived elements in the central nervous system: an immunohistochemical and ultrastructural survey of rat chimeras. J Neuropathol Exp Neurol 51:246–256

    Google Scholar 

  11. Ishii T (1969) Enzyme histochemical studies of senile plaques and the plaque-like degeneration of arteries and capillaries (Scholz). Acta Neuropathol (Berl) 14:250–260

    Google Scholar 

  12. Itagaki S, McGeer PL, Akiyama H (1988) Presence of T-cytotoxic suppressor and leucocyte common antigen-positive cells in Alzheimer disease brain tissue. Neurosci Lett 91:259–264

    Google Scholar 

  13. Kawai M, Kalaria RN, Harik SI, Perry G (1990) The relationship of amyloid plaques to cerebral capillaries in Alzheimer's disease. Am J Pathol 137:1435–1446

    Google Scholar 

  14. Lawson LJ, Perry VH, Gordon S (1992) Turnover of resident microglia in the normal adult mouse brain. Neuroscience 48:405–415

    Google Scholar 

  15. Lin F-H, Lin H, Wisniewski HM, Hwang Y-W, Grundke-Iqbal I, Healy-Louie G, Iqbal K (1992) Detection of point mutations in codon 331 of mitochondrial NADH dehydrogenase subunit 2 in Alzheimer's brains. Biochem Biophys Res Commun 182:238–246

    Google Scholar 

  16. Ling EA (1981) The origin and nature of microglia. In: Fedoroff S, Hertz L (eds) Advances in cellular neurobiology, vol 2. Academic Press, New York, pp 33–82

    Google Scholar 

  17. Miyakawa T, Shimoji A, Kumamoto R, Higuchi Y (1982) 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] 40:121–129

    Google Scholar 

  18. Murabe Y, Sano Y (1982) Morphological studies on neuroglia. IV. Postnatal development of microglial cells. Cell Tissue Res 225:464–485

    Google Scholar 

  19. Neve RL, Finch EA, Dawes LP (1988) Expression of the Alzheimer amyloid protein gene transcripts in the human brain. Neuron 1:669–677

    Google Scholar 

  20. Perry VH, Gordon S (1987) Modulation of CD4 antigen on macrophages and microglia in rat brain. J Exp Med 166:1138–1143

    Google Scholar 

  21. Perry VH, Crocker RP, Gordon S (1992) The blood-brain barrier regulates the expression of a macrophage sialic acidbinding receptor on microglia. J Cell Sci 101:201–207

    Google Scholar 

  22. Streit WJ, Graeber MB, Kreutzberg GW (1989) Expression of la antigen on perivascular and microglial cells after sublethal and lethal motor neuron injury. Exp Neurol 105:115–126

    Google Scholar 

  23. Tseng CY, Ling EA, Wong WC (1983) Scanning electron microscopy of ameboid microglial cells in the transient cavum septum pellucidum in pre-and postnatal rats. J Anat 136:251–263

    Google Scholar 

  24. Wegiel J, Wisniewski HM (1990) The complex of microglial cells and amyloid star in three-dimensional reconstruction. Acta Neuropathol 81:116–124

    Google Scholar 

  25. Wisniewski HM, Moretz RC, Lossinsky AS (1981) Evidence for induction of localized amyloid deposits and neuritic plaques by an infectious agent. Ann Neurol 10:517–522

    Google Scholar 

  26. Wisniewski HM, Wegiel J, Wang KC, Kujawa M, Lach B (1989) Ultrastructural studies of the cells forming amyloid fibers in classical plaques. Can J Neurol Sci 16:535–542

    Google Scholar 

  27. Wisniewski HM, Vorbrodt AW, Wegiel J, Morys J, Lossinsky AS (1990) Ultrastructure of the cells forming amyloid fibers in Alzheimer disease and scrapie. Am J Med Genet [Suppl] 7:287–297

    Google Scholar 

  28. Wisniewski H, Wegiel J, Strojny P, Wang K-C, Kim K-S, Burrage T (1991) Ultrastructural morphology and immunocytochemistry of beta amyloid classical, primitive and diffuse plaque. In: Ishii T, et al (eds) Frontiers of Alzheimer research. Elsevier, Amsterdam, pp 99–108

    Google Scholar 

  29. Wisniewski HM, Wegiel J, Vorbrodt AW, Barcikowska M, Burrage TG (1991) The cellular basis for β-amyloid fibril formation and removal. In: Iqbal K, McLachlan DRC, Winblad B, Wisniewski HM (eds) Alzheimer's disease: basic mechanisms, diagnosis and therapeutic strategies. John Wiley and Sons, Chichester, pp 333–339

    Google Scholar 

  30. Wisniewski HM, Wegiel J, Wang KC, Lach B (1992) Ultrastructural studies of the cells forming amyloid in the cortical vessel wall in Alzheimer's disease. Acta Neuropathol 84:117–127

    Google Scholar 

  31. Wisniewski HM, Wegiel J, Kozlowski P (1992) Microglia in scrapie. In: Liberski PP (ed) Light and electron microscopic neuropathology of slow virus disorders. CRC Press, Boca Raton, pp 251–268

    Google Scholar 

  32. Zoltowska A (1991) Myoid and epithelial cell differentiation in myasthenic thymuses. Thymus 17:237–248

    Google Scholar 

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Supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and a grant from the National Institutes of Health, National Institute of Aging No. PO1-AGO-4220

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Wisniewski, H.M., Weigel, J. Migration of perivascular cells into the neuropil and their involvement in β-amyloid plaque formation. Acta Neuropathol 85, 586–595 (1993). https://doi.org/10.1007/BF00334667

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  • DOI: https://doi.org/10.1007/BF00334667

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