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Development of α-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease

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Abstract

Astrocytic α-synuclein-immunoreactive inclusions have recently been noted to develop in sporadic Parkinson’s disease (PD). Here, the presence of immunoreactive astrocytes is reported in 14 autopsy cases with clinically diagnosed PD and a neuropathological stage of 4 or higher. The labeled astrocytes occur preferentially in prosencephalic regions (amygdala, thalamus, septum, striatum, claustrum, and cerebral cortex). They appear first in layers V–VI of the temporal mesocortex, then in the striatum and in thalamic nuclei that project to the cortex. The topographical distribution pattern of these astrocytes closely parallels that of the cortical intraneuronal Lewy neurites and Lewy bodies, which, from their foothold in the mesocortex, gradually encroach upon neocortical association areas and even the primary fields. Thus, labeling of astrocytes appears to accompany the formation of neuronal inclusion bodies. Relatively small immunoreactive cortical pyramidal neurons in layers V–VI probably project to nearby destinations, such as the striatum and thalamus. Inasmuch as the projection neurons of both the striatum and the dorsal thalamus do not develop Lewy bodies, it is suggested that the most likely cause of the astrocytic reaction may be a slightly altered α-synuclein molecule that escapes from terminal axons of affected cortico-striatal or cortico-thalamic neurons and is taken up by astrocytes. Other aggregated proteins known to co-occur with PD-associated intraneuronal lesions, e.g., Aβ protein or neurofibrillary changes of the Alzheimer type, do not appear to influence the development of the α-synuclein immunoreactive astrocytes.

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Acknowledgments

This study was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG) and by funding from the Hilde-Ulrichs-Stiftung, Florstadt-Staden, Germany. The authors have no existing or pending conflicts of interest. Autopsies were performed in compliance with ethics committee guidelines of participating institutions. We thank Mr. Mohamed Bouzrou (laboratory technical assistance) and Ms. Inge Szász-Jacobi (graphics) for adept technical support. The Afshp antibody was generously supplied by Dr. Wei Ping Gai (Department of Human Physiology, Flinders Medical Centre, Bedford Park, SA, Australia).

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  1. Institute for Clinical Neuroanatomy, J.W. Goethe University, Theodor Stern Kai 7, 60590, Frankfurt am Main, Germany

    Heiko Braak & Kelly Del Tredici

  2. Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany

    Magdalena Sastre

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Braak, H., Sastre, M. & Del Tredici, K. Development of α-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease. Acta Neuropathol 114, 231–241 (2007). https://doi.org/10.1007/s00401-007-0244-3

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