Development of α-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease
Abstract
Astrocytic alpha-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 alpha-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…
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The α-syn transgenic mouse model overexpressing human wild-type α-synuclein under the murine Thy1 promoter reproduces most features of synucleinopathies, including neuropathology and deficits in motor and non-motor function.
“The mouse model utilized in current study is known to reproduce most features of synucleinopathies, including neuropathology and deficits in motor and non-motor function (46).”
From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [44]
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- Authors
- Braak, H., Sastre, M., & Del Tredici, K.
- Affiliations
- Goethe University Frankfurt (DE)
- University of Bonn (DE)
- Corresponding author
- Braak, Heiko
- Venue
- Acta Neuropathologica
- Published
- 2007-06-19
- Volume
- 114
- Issue
- 3
- Pages
- 231-241
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2070953412
- Cited by
- 462
- References
- 8
- Citations by year
- 2026: 12 · 2025: 32 · 2024: 35 · 2023: 30 · 2022: 54 · 2021: 34 · 2020: 46 · 2019: 30 · 2018: 29 · 2017: 27 · 2016: 11 · 2015: 31 · 2014: 20 · 2013: 8 · 2012: 14
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- alpha-synuclein, astrocytes, Parkinson's disease, Lewy bodies, Lewy neurites, forebrain, amygdala, thalamus, striatum, astrocytic reaction, neuropathological staging
- MeSH terms
- Aged, Aged, 80 and over, Astrocytes, Inclusion Bodies, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neurons, Parkinson Disease, Prosencephalon, Lewy Bodies, alpha-Synuclein
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