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Simultaneous imaging of redox states in dystrophic neurites and microglia at Aβ plaques indicate lysosome accumulation not microglia correlate with increased oxidative stress
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Accumulation of lysosomes around amyloid β plaques is associated with increased oxidative stress.
“Additionally, accumulation of lysosomes around Aβ plaques is associated with increased oxidative stress (Wendt et al., 2022).”
From Hippocampal TMEM55B overexpression in the 5XFAD mouse model of Alzheimer's disease (2024) · cites this paper as Wendt et al., 2022
Dysfunction of the endosomal-lysosomal system is directly linked with oxidative stress.
“Dysfunction of the endosomallysosomal system is also directly linked with Aβ deposition (Lee et al., 2022), oxidative stress (Wendt et al., 2022), and synaptic dysfunction (Adalbert et al., 2009).”
From Hippocampal TMEM55B overexpression in the 5XFAD mouse model of Alzheimer's disease (2024) · cites this paper as Wendt et al., 2022
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“In the 5xFAD mouse model of severe amyloidosis and AD, the overproduction of Aβ1-42 is the key process triggering the AD pathology observed in these animals [34] suggesting that Aβ itself may also trigger the cascade that leads to Ox-stress in DNs surrounding plaques.”
BackgroundMethodInfluentialOxidative stress and the amyloid beta peptide in Alzheimer’s disease
Cheignon, C., Tomas, M., Bonnefont-Rousselot, D., Faller, P., Hureau, C., & Collin, F. (2018) · Redox Biology · doi:10.1016/j.redox.2017.10.014 · Cited by 2,185
Microglia in Alzheimer’s disease
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“Microglia, the primary immune cells of the brain express many AD risk genes [16] and accumulate around Aβ plaques in human AD patients and in AD mouse models.”
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“Therefore we performed IHC imaging of other potential contributors to ROS generation at Aβ plaques to investigate their correlation with increased Ox-stress as a first step to evaluating their potential as candidates for generating Ox-stress when microglia are partially depleted [23,24].”
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“amyloidosis leads to increased plaque loads with memory deficits and neuronal loss as early as 9 months of age [34,48].”
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“These data indicate that microglia are not the primary source of neuronal Ox-stress in DNs surrounding Aβ plaques and further suggest that neuroprotective as well as neurotoxic phenotypes of microglia act in parallel since removal of microglia also reduces neuronal loss and improves memory formation [36,37].”
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Detection and Clearance of Damaged Lysosomes by the Endo-Lysosomal Damage Response and Lysophagy
Papadopoulos, C., & Meyer, H. (2017) · Current Biology · doi:10.1016/j.cub.2017.11.012 · Cited by 230 · cited 2×
“the presence of dysfunctional lysosomes in these structures [41,42].”
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Bernier, L.-P., Bohlen, C. J., York, E. M., Choi, H. B., Kamyabi, A., Dissing-Olesen, L., Hefendehl, J. K., Collins, H. Y., Stevens, B., Barres, B. A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.010 · Cited by 211
Self-citationRapid cell death is preceded by amyloid plaque-mediated oxidative stress
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Oskar Fischer and the study of dementia
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Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
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“neuron-microglia interaction remains unknown [17].”
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Sorted by citations
Hippocampal TMEM55B overexpression in the 5XFAD mouse model of Alzheimer's disease
Odfalk, K. F., Wickline, J. L., Smith, S., Dobrowolski, R., & Hopp, S. C. (2024) · Hippocampus · doi:10.1002/hipo.23586 · Cited by 2
Metadata
- Authors
- Wendt, S., Johnson, S., Weilinger, N. L., Groten, C., Sorrentino, S., Frew, J., Yang, L., Choi, H. B., Nygaard, H. B., & MacVicar, B. A.
- ORCID
- Wendt, Stefan
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 56
- Pages
- 102448
- ISSN
- 2213-2317
- PMC
- PMC9440309
- Cited by
- 20
- References
- 24
- Language
- en
- Licence
- Funders
- Deutsche Forschungsgemeinschaft (6264/2-2, WE 6264/2-2)
- Canadian Institutes of Health Research (FDN148397, 148397)
- Alzheimer's Association (AARF-21-848318, -21-848318)
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