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Reelin-immunoreactive Cajal-Retzius cells: the entorhinal cortex in normal aging and Alzheimer's disease

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Abstract

Alzheimer's disease (AD) is a disorder of brain self organization associated with morphodysregulation at the synaptic level. Disturbances follow a hierarchical spatio-temporal pattern throughout the cortex and involve the re-activation of developmental molecular programs. The large glycoprotein reelin, synthesized by Cajal-Retzius (CR) cells, is an important component of a signaling pathway involved in embryonic development and modulation of synaptic circuitry, but is also implicated in the pathogenetic cascade in AD. Although the majority of CR cells sequentially disappears from the postnatal cortical layer I, a few of them persist in the normal adult brain. They continue to produce reelin, express a variety of other proteins, and are characterized by a typical morphology. Recently, CR cells have been reported to be altered in number and morphology in a variety of neurological and psychiatric diseases linked to maldevelopment. In the present study we show that reelin-positive CR cells persist in the layer I of the entorhinal cortex in normal senescent brains and are also preserved in AD. The majority of CR cells in AD is morphologically and cytochemically—as revealed by double labeling with calcium-binding proteins—indistinguishable from normal cases, suggesting that they are not dramatically altered in the entorhinal cortex of AD patients. Nevertheless, CR cells seem to be partially affected by the formation of paired helical filaments, indicating subtle changes that are suggested to be a result rather than a cause of the pathogenetic cascade of AD.

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Acknowledgements

We thank Dr. A.M. Goffinet (University of Namur Medical School, Belgium) for the generous donation of the reelin antibody mAb 142. Mrs. H. Gruschka (University of Leipzig), Mrs. T. Kauppinen and Mrs. A.-L. Gidlund (University of Kuopio) are warmly acknowledged for their excellent technical assistance. Supported by the Bundesministerium für Bildung und Forschung (program NBL3, No.: 01ZZ0106); the European Commission (Project QLK6-CT-1999-02112); the Health Research Council of the Academy of Finland; Deutscher Akademischer Austauschdienst (DAAD, Project 313-SF-ppp-7–00/1); and Interdisziplinäres Zentrum für Klinische Forschung (IZKF) at the University of Leipzig (01KS9504, Project C1).

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  1. Department of Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany

    Anett Riedel, Jens Stieler & Thomas Arendt

  2. Departments of Neurology and Neurosciences and Pathology, University and University Hospital of Kuopio, P. O. Box 1627, 70211, Kuopio, Finland

    Riitta Miettinen, Mia Mikkonen, Irina Alafuzoff & Hilkka Soininen

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  1. Anett Riedel
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Riedel, A., Miettinen, R., Stieler, J. et al. Reelin-immunoreactive Cajal-Retzius cells: the entorhinal cortex in normal aging and Alzheimer's disease. Acta Neuropathol 106, 291–302 (2003). https://doi.org/10.1007/s00401-003-0729-7

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