Summary
The ultrastructural localization of amyloidβ/ A4 protein precursor (APP) was studied immunohistochemically in normal rat brains using antibodies against different portions of APP. In cerebral cortical neurons and Purkinje cells, APP reaction products were located in the cytoplasm and on cell surface membranes. Some Golgi apparatuses and rough endoplasmic reticulum also showed APP immunoreactivity on their membranes and some vesicles near the trans face of the Golgi apparatuses were stained. In the neuropil of the cerebral cortex and the cerebellar molecular layer, many cell processes, which surrounded synapses and were considered to be astrocytic, were APP-positive. Foot processes around capillaries and subpial astrocytic processes were also immuno-positive. At the ultrastructural level, APP-positive astrocytic processes were identified.
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References
Bahmanyer S, Higgins GA, Goldgaber D, Lewis DA, Morrison JH, Wilson MC, Shanker SK, Gajdusek DC (1987) Localization of amyloidβ protein messenger RNA in brains from patients with Alzheimer’s disease. Science 237:77–80
Bendotti C, Forloni GL, Morgan RA, O’Hara BF, Oster-Granite ML, Reeves RH, Gearhart JD, Coyle JT (1988) Neuroanatomical localization and quantification of amyloid precursor protein mRNA by in situ hybridization in the brains of normal, aneuploid, and lesioned mice. Proc Natl Acad Sci USA 85:3628–3632
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
Card JP, Meade RP, Davis LG (1988) Immunocytochemical localization of the precursor protein for β-amyloid in the rat central nervous system. Neuron 1:835–846
Cole G, Huynh TV, Saitoh T (1989) Evidence for lysosomal processing of amyloid β-protein precursors in cultured cells. Neurochem Res 14:933–939
Chartier-Harlin M-C, Crawford 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
Esch FS, Keim PS, Beattie EC, Blacher RW, Culwell AR, Oltersdorf T, McClure D, Ward PJ (1990) Cleavage of amyloidβ peptide during constitutive processing of its precursor. Science 248:1122–1124
Frautschy SA, Baird A, Cole GM (1991) Effects of injected Alzheimer β-amyloid cores in rat brain. Proc Natl Acad Sci USA 88:8362–8366
Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890
Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, 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
Goedert M (1987) Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer’s disease. EMBO J6:3627–3532
Golde TE, Estus S, Usiak M, Younkin LH, Younkin SG (1990) Expression ofβ amyloid protein precursor mRNAs: recognition of a novel alternatively spliced form and quantitation in Alzheimer’s disease using PCR. Neuron 4:253–267
Golde TE, Estus S, Younkin LH, Selkoe DH, Younkin SG (1992) Processing of the amyloid protein precursor to potentially amyloidogenic derivatives. Science 255:728–730
Haass C, Hung AY, Selkoe DJ (1991) Processing of β-amyloid precursor protein in microglia and astrocytes favors an internal localization over constitutive secretion. J Neurosci 11:3783–3793
Haass C, Koo EH, Mellon A, Hung AY, Selkoe DJ (1992) A second processing pathway for the β-amyloid precursor protein: cell surface molecules traffic to lysosomes and generate amyloid-bearing fragments. Nature 357:500–503
Harigaya Y, Shoji M, Ishiguro K, Kanai H, Yamaguchi H, Okamoto K, Hirai S, Takatama M (1990) Secreted forms of amyloidβ protein precursor in cerebrospinal fluid and sera. Neurobiol Aging 11:308
Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill B (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733–736
Kawarabayashi T, Shoji M, Harigaya Y, Yamaguchi H, Hirai S (1991a) Amyloid β/A4 protein precursor is widely distributed in both the central and peripheral nervous systems of the mouse. Brain Res 552:1–7
Kawarabayashi T, Shoji M, Harigaya Y, Yamaguchi H, Hirai S (1991 b) Expression of APP in the early stage of brain damage. Brain Res 563:334–338
Kitaguchi N, Takahashi Y, Tokushima Y, Shiojiri S, Ito H (1988) Novel precursor of Alzheimer’s disease amyloid protein shows protease inhibitor activity. Nature 331:530–532
Kowall NW, Beal MF, Busciglio J, Duffy LK, Yankner BA (1991) An in vivo model for the neurodegenerative effects of β amyloid and protection by substance P. Proc Natl Acad Sci USA 88:7247–7251
Kubota Y, Inagaki S, Shimada S, Takagi H (1991) Spiny and aspiny types of neuropeptide Y immunoreactive neurons in the monkey neostriatum. Neurosci Lett 122:109–112
Lewis DA, Higgins GA, Young WG, Goldgaber D, Gajdusek DC, Wilson MC, Morrison JH (1988) Distribution of precursor amyloid-β-protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques. Proc Natl Acad Sci USA 85:1691–1695
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82:4245–4249
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
Neve RL, Finch EA, Dawes LR (1988) Expression of the Alzheimer amyloid precursor gene transcripts in the human brain. Neuron 1:669–677
Oltersdorf T, Ward PJ, Henriksson T, Beattie EC, Neve R, Lieberberg I, Fritz LC (1990) The Alzheimer amyloid precursor protein. Identification of a stable intermediate in the biosynthetic/ degradative pathway. J Biol Chem 265:4492–4497
Priestley JV, Alvarez FJ, Averill S (1992) Pre-embedding electron microscopic immunocytochemistry. In: Polak JM, Priestley JV (eds) Electron microscopic immunocytochemistry: principles and practice. Oxford University Press, Oxford New York Tokyo, pp 89–121
Schmechel DE, Goldgaber D, Burkhart DS, Gilbert JR, Gajdusek DC, Roses AD (1988) Cellular localization of messenger RNA encoding amyloid-beta-protein in normal tissue and in Alzheimer disease. Alzheimer Dis Assoc Dis 2:96–111
Schubert D, Cole G, Saitoh T, Oltersdorf T (1989) Amyloid beta protein precursor is a mitogen. Biochem Biophys Res Commun 162:83–88
Schubert W, Reinhard P, Weidemann A, Dircksen H, Multhap G, Masters CL, Beyreuther K (1991) Localization of Alzheimer βA4 amyloid precursor protein at central and peripheral synaptic sites. Brain Res 563:184–194
Selkoe DJ, Podlisny MB, Joachim CL, Vickers EA, Lee G, Fritz LC, Oltersdorf T (1988) β-Amyloid precursor protein of Alzheimer disease occurs as 110to 135-kirodalton membrane-associated proteins in neural and nonneural tissues. Proc Natl Acad Sci USA 85:7341–7345
Shivers BD, Hilbich C, Multhaup G, Salbaum M, Beyreuther K, Seeburg PH (1988) Alzheimer’s disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact. EMBO 7:1365–1370
Shoji M, Hirai S, Yamaguchi H, Harigaya Y, Kawarabayashi T (1990a) Amyloid β-protein precursor accumulates in dystrophic neuntes of senile plaque in Alzheimer-type dementia. Brain Res 512:164–168
Shoji M, Hirai S, Harigaya Y, Kawarabayashi T, Yamaguchi H (1990b) The amyloid β-protein precursor is localized in smooth muscle cells of leptomeningeal vessels. Brain Res 530:113–116
Shoji M, Kawarabayashi T, Harigaya Y, Yamaguchi H, Hirai S, Kamimura T, Sugiyama T (1990 c) Alzheimer amyloid β-protein precursor in sperm development. Am J Pathol 137:1027–1032
Siman R, Card JP, Nelson RB, Davis LG (1989) Expression of β-amyloid precursor protein in reactive astrocytes following neuronal damage. Neuron 3:275–285
Spllantini MG, Goedert M, Jakes R, Klug A (1990) Topographical relationship between β-amyloid and tau protein epitopes in tangle-bearing cells in Alzheimer disease. Proc Natl Acad Sci USA 87:3252–3256
Weidemann A, König G, Bunke D, Fischer P, Salbaum JM, Masters CL, Beyreuther K (1989) Identification, biogenesis, and localization of precursors of Alzheimer’s disease A4 amyloid protein. Cell 57:115–126
Yamaguchi H, Nakazato Y, Hirai S, Shoji M (1990a) Immunoelectron microscopical localization of amyloidβ protein in the diffuse plaques of Alzheimer-type dementia. Brain Res 508:320–324
Yamaguchi H, Ishiguro K, Shoji M, Yamazaki T, Nakazato Y, Ihara Y, Hirai S (1990b) Amyloid β/A4 protein precursor is bound to neurofibrillary tangles in Alzheimer-type dementia. Brain Res 537:318–322
Yamaguchi H, Nakazato Y, Yamazaki T, Shoji M, Kawarabayashi T, Hirai S (1991 a) Subpial β/A4 amyloid protein occurs between astroglial processes in the Alzheimer-type dementia. Neurosci Lett 223:217–220
Yamaguchi H, Nakazato Y, Shoji M, Okamoto K, Ihara Y, Morimatsu M, Hirai S (1991b) Secondary deposition of beta amyloid within extracellular neurofibrillary tangles in Alzheimertype dementia. Am J Pathol 138:699–705
Yamaguchi H, Nakazato Y, Shoji M, Takatama M, Hirai S (1991 c) Ultrastructure of diffuse plaques in senile dementia of the Alzheimer type: comparison with primitive plaques. Acta Neuropathol 82:13–20
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Yamazaki, T., Yamaguchi, H., Kawarabayashi, T. et al. Ultrastructural localization of amyloid β/A4 protein precursor in the normal rat brain. Virchows Archiv B Cell Pathol 63, 173–180 (1993). https://doi.org/10.1007/BF02899258
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DOI: https://doi.org/10.1007/BF02899258