The role of astrocytes in Alzheimer’s and Parkinson’s disease
Decades of research have focused on neuronal abnormalities in Alzheimer's disease (AD) and Parkinson's disease (PD), while glial cells have been given much less attention. Astrocytes, the most common type of glial cell, have significant impact on overall brain health. The aim of our research is to understand how astrocytes contribute to the propagation of AD and PD. With this new approach, we hope to pave the way for novel treatment strategies.

Changes in the AD and PD brain
In AD and PD, there is an accumulation of harmful proteins in the brain. Amyloid-beta and tau form large deposits in the AD brain, while aggregates of alpha-synuclein accumulate in the PD brain. Moreover, chronic inflammation increases during the course of the disease. Despite the fact that these pathological changes were described already a century ago, many questions remain regarding the underlying cellular mechanisms and how the disease propagates to other regions of the brain.
Astrocytes spread pathological protein aggregates
Our research demonstrate that astrocytes ingest and process, but fail to fully degrade aggregated amyloid-beta, tau, and alpha-synuclein. Instead, the protein aggregates are stored as large deposits in the astrocytes, which causes inflammation and cellular dysfunction. Importantly, we have shown that stressed astrocytes spread pathogenic protein aggregates to nearby cells via different routes. For example, astrocytes contact their neighbors with thin thread-like projections (nanotubes) and release vesicles containing partially degraded material, which cause damage to surrounding neurons. Taken together, our results indicate that astrocytes could be a potential treatment target for AD and PD.
Methods
To investigate how astrocytes affect various pathological processes, we have developed useful 2D and 3D disease models, based on human iPSC-derived astrocytes, neurons, and microglia. Using a battery of techniques, including live cell imaging, flow cytometry and immunostainings, as well as protein and lipid analyses, we are uncovering astrocyte-mediated disease mechanisms.
Publications
Part of Acta neuropathologica communications, 2024
- DOI for Altered amyloid-β structure markedly reduces gliosis in the brain of mice harboring the Uppsala APP deletion
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Amyloid-β deposits in human astrocytes contain truncated and highly resistant proteoforms
Part of Molecular and Cellular Neuroscience, 2024
- DOI for Amyloid-β deposits in human astrocytes contain truncated and highly resistant proteoforms
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Part of Acta neuropathologica communications, 2024
- DOI for Astrocytic accumulation of tau fibrils isolated from Alzheimer’s disease brains induces inflammation, cell-to-cell propagation and neuronal impairment
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Tau processing and tau-mediated inflammation differ in human APOEε2 and APOEε4 astrocytes
Part of iScience, 2024
- DOI for Tau processing and tau-mediated inflammation differ in human APOEε2 and APOEε4 astrocytes
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Part of Cellular and molecular neurobiology, p. 3023-3035, 2023
- DOI for Altered Distribution of SNARE Proteins in Primary Neurons Exposed to Different Alpha-Synuclein Proteoforms
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Part of Journal of Neuroinflammation, 2023
- DOI for Amyloid-beta accumulation in human astrocytes induces mitochondrial disruption and changed energy metabolism
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Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology
Part of Acta neuropathologica communications, 2023
- DOI for Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology
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Part of Journal of Neuroinflammation, 2023
- DOI for Intracellular deposits of amyloid-beta influence the ability of human iPSC-derived astrocytes to support neuronal function
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Long-term effects of amyloid-beta deposits in human iPSC-derived astrocytes
Part of Molecular and Cellular Neuroscience, 2023
- DOI for Long-term effects of amyloid-beta deposits in human iPSC-derived astrocytes
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Part of Molecular Therapy Nucleic Acids, p. 450-461, 2022
- DOI for CRISPR-Cas9 treatment partially restores amyloid-β 42/40 in human fibroblasts with the Alzheimer's disease PSEN1 M146L mutation
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Part of Neurobiology of Aging, p. 207-220, 2021
- DOI for Age-related increase of alpha-synuclein oligomers is associated with motor disturbances in L61 transgenic mice
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Part of Journal of Neuroinflammation, 2021
- DOI for Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates
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Part of Theranostics, p. 789-804, 2021
- DOI for Enhanced neprilysin-mediated degradation of hippocampal A beta 42 with a somatostatin peptide that enters the brain
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Parkinson's Disease-Associated LRRK2 Interferes with Astrocyte-Mediated Alpha-Synuclein Clearance
Part of Molecular Neurobiology, p. 3119-3140, 2021
- DOI for Parkinson's Disease-Associated LRRK2 Interferes with Astrocyte-Mediated Alpha-Synuclein Clearance
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Part of Science Translational Medicine, 2021
Part of Scientific Reports, 2021
- DOI for Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy
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Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson's disease brain
Part of Journal of Neuroinflammation, 2020
- DOI for Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson's disease brain
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Part of Scientific Reports, 2020
- DOI for Extracellular vesicles from amyloid-beta exposed cell cultures induce severe dysfunction in cortical neurons
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Part of Biomedicine and Pharmacotherapy, 2020
- DOI for Prolyl oligopeptidase inhibition by KYP-2407 increases alpha-synuclein fibril degradation in neuron-like cells
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Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease
Part of Journal of Alzheimer's Disease, p. 161-180, 2019
- DOI for Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease
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