Strong immunoreactivity of β-amyloid precursor protein, including the β-amyloid protein sequence, at human neuromuscular junctions

Abstract At the postsynaptic domain of the human neuromuscular junction (NMJ), we have demonstrated strong concentrations of the N-terminus 45–62, C-terminus 676–695 and β-amyloid protein sequences of β-amyloid precursor protein (βAPP). We used well-characterized monoclonal and polyclonal antibodies for co-localization with three other postsynaptic proteins, applying double and triple fluorescence labeling. Strong immunoreactivity of all three βAPP sequences was found at all NMJs identified by bound α-bungarotoxin (αBT), where they co-localized with αBT and with immunoreactive desmin and dystrophin, which are postsynaptic proteins of human NMJs. This appears to be the first demonstration of βAPP sequences concentrated postsynaptically at human NMJs. βAPP may have a role in normal junctional biology and possibly in some diseases affecting NMJs.

[1]  S. Froehner.  The submembrane machinery for nicotinic acetylcholine receptor clustering , 1991, The Journal of cell biology.

[2]  W. Engel,et al.  Light and electron microscopic localization of beta-amyloid protein in muscle biopsies of patients with inclusion-body myositis. , 1992, The American journal of pathology.

[3]  G. Glenner,et al.  Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein , 1984 .

[4]  W. Engel,et al.  β-amyloid protein immunoreactivity in muscle of patients with inclusion-body myositis , 1992, The Lancet.

[5]  K. Grzeschik,et al.  The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor , 1987, Nature.

[6]  P. S. St George-Hyslop,et al.  Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. , 1987, Science.

[7]  L. Refolo,et al.  The Alzheimer amyloid precursor is associated with the detergent- insoluble cytoskeleton , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  B. Greenberg,et al.  A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors , 1988, Nature.

[9]  D. Selkoe,et al.  Amyloid β-protein deposition in tissues other than brain in Alzheimer's disease , 1989, Nature.

[10]  G. Multhaup,et al.  Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease. , 1988, The EMBO journal.

[11]  W. Engel,et al.  Immunocytochemical localization of ubiquitin at human neuromuscular junctions , 1992, Neuropathology and applied neurobiology.

[12]  N. Robakis,et al.  The Alzheimer's amyloid precursor protein is produced by type I astrocytes in primary cultures of rat neuroglia , 1990, Journal of neuroscience research.

[13]  Walter Schubert,et al.  Localization of Alzheimer βA4 amyloid precursor protein at central and peripheral synaptic sites , 1991, Brain Research.

[14]  C. Masters,et al.  Amyloid plaque core protein in Alzheimer disease and Down syndrome. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[15]  K. Beyreuther,et al.  Ultrastructural localization of the putative precursors of the A4 amyloid protein associated with Alzheimer's disease. , 1990, The American journal of pathology.

[16]  L. Villa-komaroff,et al.  Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease , 1988, Nature.

[17]  W. Engel.  Muscle biopsies in neuromuscular diseases. , 1967, Pediatric clinics of North America.

[18]  F. Tagliavini,et al.  Coexistence of Alzheimer's amyloid precursor protein and amyloid protein in cerebral vessel walls. , 1990, Laboratory investigation; a journal of technical methods and pathology.

[19]  C. Masters,et al.  Localization of the putative precursor of Alzheimer's disease‐specific amyloid at nuclear envelopes of adult human muscle. , 1988, The EMBO journal.

[20]  The regulation of amyloid β protein precursor secretion and its modulatory role in cell adhesion , 1989, Neuron.

[21]  W. Engel,et al.  Immunocytochemical localization of desmin at human neuromuscular junctions , 1990, Neurology.

[22]  W. Engel,et al.  Immunolocalization of ubiquitin in muscle biopsies of patients with inclusion body myositis and oculopharyngeal muscular dystrophy , 1991, Neuroscience Letters.

[23]  Andreas Weidemann,et al.  Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein , 1989, Cell.

[24]  J. Marx.  Boring in on beta-amyloid's role in Alzheimer's. , 1992, Science.

[25]  B. Anderton,et al.  Beta amyloid precursor protein mediates neuronal cell‐cell and cell‐surface adhesion , 1991, Journal of neuroscience research.

[26]  D. Selkoe,et al.  Isolation of Low‐Molecular‐Weight Proteins from Amyloid Plaque Fibers in Alzheimer's Disease , 1986, Journal of neurochemistry.

[27]  G. Glenner,et al.  Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[28]  D. Selkoe,et al.  Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[29]  G. Cole,et al.  Amyloid β-protein precursor is associated with extracellular matrix , 1990, Brain Research.

[30]  G. Multhaup,et al.  Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact. , 1988, The EMBO journal.

[31]  D. Selkoe.  The molecular pathology of Alzheimer's disease , 1991, Neuron.