Summary
The origin of the extracellular β-amyloid protein (β/A4) found in senile plaques and the cellular mechanisms responsible for its deposition in cerebral tissues are still an unresolved issue in Alzheimer's disease. In this study we analyzed in detail the distribution of various epitopes of β/A4 in relation to local cellular elements in diffuse plaques of the hippocampal region. We also correlated our findings with the presence and distribution of non-β/A4 epitopes of the amyloid precursor protein (APP) and with synaptophysin immunoreactivity in the cortical neuropil. Discontinuous β/A4-immunoreactive deposits were found along dendrites, and around the soma of neurons included in the plaques. Furthermore, increased synaptophysin reactivity with slightly dilated synaptophysin-immunolabeled presynaptic terminals were found in diffuse plaques. APP epitopes could not be found in diffuse plaques. However, some of the APP antibodies, mainly those to the C-terminal portion of APP, and antibodies to β/A4 recognized clusters of flat vesicular profiles (0.6–1.4 μm in width and 2–3 μm in length) in the neuropil of cortical areas where plaques had developed. Our findings are compatible with a neuronal origin of β/A4 in diffuse plaques and with a primary release of β/A4 at synaptic sites along the immunostained neurites. They also suggest that diffuse plaques might be preceded by minute lesions of the neuropil where β/A4 is not yet released from the precursor molecule.
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Allsop D, Haga SI, Haga C, Ikeda SI, Mann DMA, Ishii T (1989) Early senile plaques in Down's syndrome brains show a close relationship with cell bodies of neurons. Neuropathol Appl Neurobiol 15:531–542
Anderson JP, Refolo LM, Wallace W, Mehta P, Krishnamurthi M, Gotlib J, Bierer L, Haroutunian V, Perl D, Robakis NK (1989) Differential brain expression of the Alzheimer's amyloid precursor protein. EMBO J 8:3627–3632
Bahmanyar S, Higgins GA, Goldgaber D, Lewis DA, Morrison JH, Wilson MC, Shankar SK, Gajdusek DC (1987) Localization of β protein messenger RNA in brains from patients with Alzheimer's disease. Science 237:77–80
Blinzinger K, Kreuzberg G (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z Zellforsch Mikrosk Anat 85:145–157
Brion JP, Couck AM, Bruce M, Anderton B, Flament-Durand J (1991) Synaptophysin and chromogranin A immunoreactivities in senile plaques of Alzheimers disease. Brain Res 539:143–150
Bugiani O, Giacone G, Verga L, Pollo B, Frangione B, Tagliavini F (1990) Alzheimer patients and Down patients: abnormal presynaptic terminals are related to cerebral preamyloid deposits. Neurosci Lett 119:56–59
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
Esch FS, Keim PS, Beattie EC, Blacher RW, Culwell AR, Oltersdorf T, McClure D, Ward P (1990) Cleavage of amyloid β peptide during constitutive processing of its precursor. Science 248:1122–1124
Glenner GG (1979) Congophilic microangiopathy in the pathogenesis of Alzheimer's syndrome (presenile dementia). Medical Hypotheses 5:1231–1236
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
Goedert M (1987) Neuronal localization of amyloid β protein precursor mRNA in normal human brain and in Alzheimer's disease. EMBO J 6:3627–3632
Higgins GA, Lewis DA, Bahmanyar S, Goldgaber DC, Gajdusek C, Young WG, Morrison JH, Wilson MD (1988) Differential regulation of amyloid-β-protein mRNA expression within hippocampal neuronal subpopulations in Alzheimer's disease. Proc Natl Acad Sci USA 85:1297–1301
Ikeda SI, Allsop D, Glenner GG (1989) Morphology and distribution of plaque and related deposits in the brain of Alzheimer's disease and control cases. An immunohistochemical study using amyloid β-protein antibody. Lab Invest 60:113–122
Jones DB (1957) Nephrotic glomerulonephritis. Am J Pathol 33:313–329
Khachaturian Z (1985) Diagnosis of Alzheimer's disease. Arch Neurol 52:1095–1105
Koo EK, Sisodia SS, Archer DR, Martin LJ, Weidemann A, Beyreuter K, Fischer P, Masters CL, Price DL (1990) Precursor of amyloid protein in Alzheimer's disease undergoes fast anterograde axonal transport. Proc Natl Acad Sci USA 87:1561–1565
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 methods. Neuropathol Appl Neurobiol 15:317–329
Masliah E, Terry RD, Mallory M, Alford M, Hansen LA (1990) Diffuse plaques do not accentuate synapse loss in Alzheimer's disease. Am J Pathol 137:1293–1297
Masters CL, Beyreuther K (1987) Neuronal origin of cerebral amyloidogenic proteins: their role in Alzheimer's disease and unconventional virus disease of the nervous system. In: Selective neuronal death. Ciba Found Symp 126:49–64
Masters CL, Mulhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K (1985) 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 4:2757–2763
Mattiace LA, Davies P, Yen SH, Dickson DW (1990) Microglia in cerebellar plaques in Alzheimer's disease. Acta Neuropathol 80:493–498
Miyakawa T, Shimoji A, Kuramoto 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
Ogomori K, Kitamoto T, Tateishi J, Sato Y, Suetsugu M, Abe M (1989) β-Protein amyloid is widely distributed in the central nervous system of patients with Alzheimer's disease. Am J Pathol 134:243–251
Probst A, Brunnschweiler H, Lautenschlager C, Ulrich J, (1987) A special type of senile plaque, possibly an initial stage. Acta Neuropathol (Berl) 74:133–141
Rozemuller JM, 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 Neurology 48:674–691
Selkoe DJ (1989) Molecular pathology of amyloidogenic proteins and the role of vascular amyloidosis in Alzheimer's disease. Neurobiol Aging 10:387–395
Selkoe DJ, Abraham CR, Podlisny MB, Duffy LK (1986) Isolation of low-molecular-weight proteins from amyloid plaque fibers in Alzheimer's disease. J Neurochem 146:1420–1434
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
Soniat TTL (1941) Histogenesis of senile plaques. Arch Neurol 46:101–114
Streit WJ, Graeber MB, Kreutzberg GW (1988) Functional plasticity of microglia: a review. Glia 1:301–307
Tagliavini F, Giaccone G, Frangione B, Bugiani O (1988) Pre-amyloid deposits in the cerebral cortex of patients with Alzheimer's disease and non demented individuals. Neurosci Lett 93:191–196
Wiedenmann B, Franke WW (1985) Identification and localization of synaptophysin, an integral membrane glycoprotein of M r 38,000 characteristic of presynaptic vesicles. Cell 41:1017–1026
Wisniewski HM, Terry RD (1973) Re-examination of the pathogenesis of the senile plaque. Prog Neuropathol 2:1–26
Wisniewski HM, Bancher C, Barcikowska M, Wen GY, Curie J (1989) Spectrum of morphological appearances of amyloid deposits in Alzheimer's disease. Acta Neuropathol 78:337–347
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
Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Nakazato (1988) Diffuse type of senile plaques in the brains of Alzheimer-type dementia. Acta Neuropathol 77:113–119
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
Yamaguchi H, Nakazato Y, Hirai S, Shoji M (1990) Immunoelectron microscopic localization of amyloid β protein in the diffuse plaques of the Alzheimer-type dementia. Brain Res 508:320–324
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Probst, A., Langui, D., Ipsen, S. et al. Deposition of β/A4 protein along neuronal plasma membranes in diffuse senile plaques. Acta Neuropathol 83, 21–29 (1991). https://doi.org/10.1007/BF00294426
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DOI: https://doi.org/10.1007/BF00294426