Abstract
The distribution of the calcium-binding protein calretinin was investigated by immunohistochemistry in the hippocampus, the subicular areas, and the entorhinal cortex in patients with Alzheimer's disease and in control subjects. By double immunolabelling, the calretinin immunoreactivity was compared to the immunoreactivity for β/A4 amyloid or for tau proteins. Calretinin-positive neurons were mainly observed in the molecular layer of the gyrus dentatus, the stratum radiatum of the Ammon's horn, and in layers II and III of the entorhinal cortex. The general pattern of calretinin immunoreactivity was conserved in Alzheimer's disease. Calretinin-positive neurons appeared normal in the hippocampus but had a reduced dendritic tree in the entorhinal cortex. Dystrophic calretinin immunoreactive fibres were often observed in the outer molecular layer of the gyrus dentatus and in the CA4 sector in Alzheimer's disease. Most neurons containing neurofibrillary tangles were not calretinin immunoreactive and most senile plaques were not associated with calretinin positive fibres. These results show that entorhinal calretinin-positive neurons are affected in Alzheimer's disease in spite of an absence of systematic association with neurofibrillary tangles and senile plaques.
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Acsady L, Halasy K, Freund TF (1993) Calretinin is present in non-pyramidal cells of the rat hippocampus. III. Their inputs from the median raphe and medial septal nuclei. Neuroscience 52: 829–841
Baimbridge KG, Celio MR, Rogers JH (1992) Calcium-binding proteins in the nervous system. Trends Neurosci 15: 303–308
Benzing WC, Brady DR, Mufson EJ, Armstrong DM (1993) Evidence that transmitter-containing dystrophic neurites precede those containing paired helical filaments within senile plaques in the entorhinal cortex of nondemented elderly and Alzheimer's disease patients. Brain Res 619: 55–68
Braak H, Braak E (1992) The human entorhinal cortex: normal morphology and lamina-specific pathology in various diseases. Neurosci Res 15: 6–31
Brion JP, Passareiro H, Nunez J, Flament-Durand J (1985) Mise en évidence immunologique de la protéine tau au niveau des lésions de dégénérescence neurofibrillaire de la maladie d'Alzheimer. Arch Biol (Brux) 95: 229–235
Brion JP, Guilleminot J, Couchie D, Nunez J (1988) Both adult and juvenile tau microtubule-associated proteins are axon specific in the developing and adult rat cerebellum. Neuroscience 25: 139–146
Brion JP, Hanger DP, Couck AM, Anderton BH (1991) A68 proteins in Alzheimer's disease are composed of several tau isoforms in a phosphorylated state which affects their electrophoretic mobilities. Biochem J 279: 831–836
Buell SJ, Coleman PD (1979) Dendritic growth in the aged human brain and failure of growth in senile dementia. Science 206: 854–856
Celio MR (1990) Calbindin D-28K and parvalbumin in the rat nervous system. Neuroscience 35: 375–475
Enderlin S, Norman AW, Celio MR (1987) Ontogeny of the calcium-binding protein calbindin D-28K in the rat nervous system. Anat Embryol (Berl) 177: 15–28
Ferrer I, Guionnet N, Cruz-Sánchez F, Tuñón T (1990) Neuronal alterations in patients with dementia: a Golgi study on biopsy samples. Neurosci Lett 114: 11–16
Ferrer I, Zújar MJ, Rivera R, Soria M, Vidal A, Casas R (1993) Parvalbumin-immunoreactive dystrophic neurites and aberrant sprouts in the cerebral cortex of patients with Alzheimer's disease. Neurosci Lett 158: 163–166
Flament S, Delacourte A, Hémon B, Défossez A (1989) Characterization of two pathological tau protein variants in Alzheimer brain cortices. J Neurol Sci 92: 133–141
Geddes JW, Anderson KJ, Cotman CW (1986) Senile plaques as aberrant sprout-stimulating structures. Exp Neurol 94: 767–776
Glezer II, Hof PR, Morgane PJ (1992) Calretinin-immunoreactive neurons in the primary visual cortex of dolphin and humans brains. Brain Res 595: 181–188
Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI (1986) Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83: 4913–4917
Gulyas AI, Miettinen R, Jacobowitz DM, Freund TF (1992) Calretinin is present in non-pyramidal cells of the rat hippocampus. I. A new type of neuron specifically associated with the Mossy fibre system. Neuroscience 48: 1–27
Hardy JA, Higgins GA (1992) Alzheimer's disease: the amyloid cascade hypothesis. Science 256: 184–185
Hasegawa M, Morishima-Kawashima M, Takio K, Suzuki M, Titani K, Ihara Y (1992) Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain. J Biol Chem 267: 17047–17054
Heizmann CW, Braun K (1992) Changes in Ca2+-binding proteins in human neurodegenerative disorders. Trends Neurosci 15: 259–264
Hof PR, Nimchinsky EA, Celio MR, Bouras C, Morrison JH (1993) Calretinin-immunoreactive neocortical interneurons are unaffected in Alzheimer's disease. Neurosci Lett 152: 145–149
Hyman BT, Van Hoesen GW, Kromer IJ, Damasio AR (1984) Alzheimers disease: cell-specific pathology isolates the hippocampal formation. Science 225: 1168–1170
Jacobowitz DM, Winsky L (1991) Immunocytochemical localization of calretinin in the forebrain of the rat. J Comp Neurol 304: 198–218
Kitamoto T, Ogomori K, Tateishi J, Prusiner SB (1987) Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloidosis. Lab Invest 57: 230–236
Kowall NW, McKee AC, Yankner BA, Beal MF (1992) In vivo neurotoxicity of beta-amyloid [β(1–40)] and the β(25–35) gragment. Neurobiol Aging 13: 537–542
Lee VMY, Balin BJ, Otvos L, Trojanowski JQ (1991) A68 proteins are major subunits of Alzheimer disease paired helical filaments and derivatized forms of normal tau. Science 251: 675–678
Lenders MB, Peers MC, Tramu G, Delacourte A, Defossez A, Petit H, Mazzuca M (1989) Dystrophic peptidergic neurites in senile plaques of Alzheimer's disease hippocampus precede formation of paired helical filaments. Brain Res 481: 344–349
Lorente de No R (1933) Studies on the structure of the cerebral cortex. I. The area entohinalis. J Psychol Neurol 45: 381–438
Lynch G, Matthews DA, Mosko S (1972) Induced acetylcholinesterase-rich layer in rat dentate gyrus following entorhinal lesions. Brain Res 42: 311–318
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer's disease and Down syndrome. Proc Natl Acad Sci USA 82: 4245–4249
Mattson MP (1990) Antigenic changes similar to those seen in neurofibrillary tangles are elicited by glutamate and Ca2+ influx in cultured hippocampal neurons. Neuron 2: 105–117
Mattson MP, Cheng B, Davis D, Bryant K, Lieberburg I, Rydel RE (1992) β-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci 12: 376–389
Miettinen R, Gulyas AI, Baimbridge KG, Jacobowitz DM, Freund TF (1992) Calretinin is present in non-pyramidal cells of the rat hippocampus. II. Co-existence with other calcium binding proteins and GABA. Neuroscience 48: 29–43
Nitsch R, Leranth C (1993) Calretinin immunoreactivity in the monkey hippocampal formation. II. Intrinsic GABAergic and hypothalamic non-GABAergic systems: an experimental tracing and co-existence study. Neuroscience 55: 797–812
Parmentier M (1990) Structure of the human cDNAs and genes coding for calbindin-D28K and calretinin. Adv Exp Med Biol 269: 27–34
Rogers JH (1987) Calretinin: a gene for a novel calcium-binding protein expressed principally in neurons. J Cell Biol 105: 1343–1353
Rogers JH (1992) Immunohistochemical markers in the rat cortex: colocalization of calretinin and calbindin-D28K with neuropeptides and GABA. Brain Res 587: 147–157
Rogers JH, Résibois A (1992) Calretinin and calbindin-D28K in rat brain: patterns of partial co-localization. Neuroscience 51: 843–865
Résibois A, Rogers JH (1992) Calretinin in rat brain: an immunohistochemical study. Neuroscience 46: 101–134
Résibois A, Blachier F, Rogers JH, Lawson DEM, Pochet R (1990) Comparison between rat brain calbindin and calretinin immunoreactivities. Adv Exp Med Biol 169: 211–214
Scheibel ME, Lindsay RD, Tomiyasu U, Scheibel AB (1976) Progressive dendritic changes in the aging human limbic system. Exp Neurol 53: 420–430
Seress L, Nitsch R, Leranth C (1993) Calretinin immunoreactivity in the monkey hippocampal formation. I. Light and electron microscopic characteristics and co-localization with other calcium-binding proteins. Neuroscience 55: 775–796
Stanfield BB, Cowan WM (1981) The sprouting of septal afferents to the dentate gyrus after lesions of the entorhinal cortex in adult rats. Brain Res 232: 162–170
Steiner B, Mandelkow E-M, Biernat J, Gustke N, Meyer HE, Schmidt B, Mieskes G, Söling HD, Drechsel D, Kirschner MW, Goedert M, Mandelkow E (1990) Phosphorylation of microtubule-associated protein tau: identification of the site for Ca2+-calmodulin-dependent kinase and relationship with tau phosphorylation in Alzheimer tangles. EMBO J 9: 3539–3544
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Supported by grants from the Belgian FRSM (3.4504.91, 3.4517.92), the “Fonds de Recherche Divry”, the “Fondation M.T. de Lava” and Alzheimer Belgique
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Brion, J.P., Résibois, A. A subset of calretinin-positive neurons are abnormal in Alzheimer's disease. Acta Neuropathol 88, 33–43 (1994). https://doi.org/10.1007/BF00294357
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DOI: https://doi.org/10.1007/BF00294357