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


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Article Info

DATE

2007-06-19

AUTHORS

Heiko Braak, Magdalena Sastre, Kelly Del Tredici

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. More... »

PAGES

231-241

References to SciGraph publications

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  • 1995-05. Cortical Lewy body-containing neurons are pyramidal cells: laser confocal imaging of double-immunolabeled sections with anti-ubiquitin and SMI32 in ACTA NEUROPATHOLOGICA
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  • 2000-01. C-terminal α-synuclein immunoreactivity in structures other than Lewy bodies in neurodegenerative disorders in ACTA NEUROPATHOLOGICA
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  • 2000-01. NACP/α-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson’s disease brains in ACTA NEUROPATHOLOGICA
  • 2006-08-01. Glial degeneration and reactive gliosis in alpha-synucleinopathies: the emerging concept of primary gliodegeneration in ACTA NEUROPATHOLOGICA
  • 1998-10. NACP/α-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy in ACTA NEUROPATHOLOGICA
  • 1994-01. Laminar origin of striatal and thalamic projections of the prefrontal cortex in rhesus monkeys in EXPERIMENTAL BRAIN RESEARCH
  • 2001. Alpha-Synuclein in NEUROPATHOLOGY AND GENETICS OF DEMENTIA
  • 1999-09. Alpha-synuclein immunoreactive Lewy bodies and Lewy neurites in Parkinson’s disease are detectable by an advanced silver-staining technique in ACTA NEUROPATHOLOGICA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00401-007-0244-3

    DOI

    http://dx.doi.org/10.1007/s00401-007-0244-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1008798849

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17576580


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