The association of astrogliosis and microglial activation with aging and Alzheimer’s disease pathology in the chimpanzee brain.
Open accessAbstract
Aging and neurodegenerative disorders, such as Alzheimer's disease (AD), trigger an immune response known as glial activation in the brain. Recent evidence indicates species differences in inflammatory responses to AD pathology, highlighting the need for additional comparative studies to further understand human‐specific neuropathologies. In the present study, we report on the occurrence of astrogliosis, microglial activation, and their relationship with age and AD‐like pathology in a cohort of male and female chimpanzees ( Pan troglodytes ). Chimpanzees with severe astrogliosis exhibited widespread upregulation of hypertrophic astrocytes immunoreactive for glial fibrillary acidic protein (GFAP) throughout all layers of the dorsolateral prefrontal cortex and a loss of the interlaminar palisade. In addition, extreme astrogliosis was associated with increased astrocyte density in the absence of significant microglial activation and AD lesions. A shift from decreased resting to increased phagocytotic microglia occurred with aging, although proliferation was absent and no changes in astrogliosis was observed. Vascular amyloid correlated with decreased astrocyte and microglia densities, while tau lesions were associated with morphological changes in microglia and greater total glia density and glia: neuron ratio. These results further our understanding of inflammatory processes within the chimpanzee brain and provide comparative data to improve our understanding of human aging and neuropathological processes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In Alzheimer's disease, ILAs lose their palisade structure, although they do not directly co-localize typical neuritic plaques.
“ILAs lose their palisade structure, although they do not directly co-localize typical neuritic plaques (Colombo et al., 2002; Edler et al., 2023).”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Edler et al., 2023
Studies on Alzheimer's disease in primates (marmosets, macaques, gorillas, and chimpanzees) showed species-specific astrocyte and microglia reactions during different astrogliosis stages, due to the different stages of the disorder.
“Studies on AD in primates (marmosets, macaques, gorillas, and chimpanzees) showed species-specific astrocyte and microglia reactions during different astrogliosis stages, due to the different stages of the disorder (Edler et al., 2023).”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Edler et al., 2023
Patients with Alzheimer's disease show a reduction in glial density at the blood-brain barrier and an increase in astrogliosis and astrocyte recruitment at inflammation sites.
“Patients with Alzheimer’s disease (AD) show a reduction in glial density at the blood-brain barrier (Webster et al., 2001), and an increase in astrogliosis and astrocyte recruitment at the inflammation sites (Edler et al., 2023).”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Edler et al., 2023
In chimpanzees, disruptions of the interlaminar palisade resemble those in human patients, associated with Aβ plaques or high levels of tau phosphorylation, often without microglia activation.
“In chimpanzees, disruptions of the interlaminar palisade resemble those in human patients, associated with Aβ plaques or high levels of tau phosphorylation, often without microglia activation.”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Edler et al., 2023
Cites
Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,992 · see citing works
Long-term cognitive impairment and functional disability among survivors of severe sepsis.
Iwashyna, T. J., Ely, E. W., Smith, D. M., & Langa, K. M. (2010) · JAMA · doi:10.1001/jama.2010.1553 · Cited by 2,582 · see citing works
Four faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,016 · cited 1× · see citing works
“…low- grade inflammation that triggers glial activation (Cotrina & Nedergaard, 2002; Dall'Olio et al., 2013; Finch, 2003; Franceschi, Bonafè, et al., 2000; Franceschi, Valensin, et al., 2000; Harman, 1956; Moller et al., 2010; Nichols et al., 1993; Poon et al., 2004; Rodier & Campisi, 2011).”
Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways
Chung, W.-S., Clarke, L. E., Wang, G. X., Stafford, B. K., Sher, A., Chakraborty, C., Joung, J., Foo, L. C., Thompson, A., Chen, C., et al. (2013) · Nature · doi:10.1038/nature12776 · Cited by 1,377 · see citing works
Imai, Y., Ibata, I., Ito, D., Ohsawa, K., & Kohsaka, S. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1112 · Cited by 872 · see citing works
Astrocytes Control Synapse Formation, Function, and Elimination
Chung, W.-S., Allen, N. J., & Eroglu, C. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020370 · Cited by 839 · see citing works
McGeer, P. L., Itagaki, S., Tago, H., & McGeer, E. G. (1987) · Neuroscience Letters · doi:10.1016/0304-3940(87)90696-3 · Cited by 836 · see citing works
Henry, C. J., Huang, Y., Wynne, A. M., & Godbout, J. P. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.09.002 · Cited by 565 · see citing works
Neuroinflammatory processes in Alzheimer’s disease
Heneka, M. T., O’Banion, M. K., Terwel, D., & Kummer, M. P. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0438-z · Cited by 433 · see citing works
The network and the remodeling theories of aging: historical background and new perspectives
Franceschi, C., Valensin, S., Bonafè, M., Paolisso, G., Yashin, A. I., Monti, D., & De Benedictis, G. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00172-8 · Cited by 335 · see citing works
Neuroinflammation in Alzheimer’s disease wanes with age
Hoozemans, J. J., Rozemuller, A. J., van Haastert, E. S., Eikelenboom, P., & van Gool, W. A. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-171 · Cited by 100 · see citing works
Perez, S. E., Raghanti, M. A., Hof, P. R., Kramer, L., Ikonomovic, M. D., Lacor, P. N., Erwin, J. M., Sherwood, C. C., & Mufson, E. J. (2013) · Journal of Comparative Neurology · doi:10.1002/cne.23428 · Cited by 95 · cited 3× · see citing works
“…astrocytes and activated microglia have been reported adjacent to Aβ and tau lesions in marmosets, macaques, gorillas, and chimpanzees (Edler et al., 2018; Härtig et al., 1997; Martin et al., 1994; Munger et al., 2019; Perez et al., 2013; Rodriguez- Callejas et al., 2016; Schultz et al., 2000).”
BackgroundSelf-citationMarlatt, M. W., Bauer, J., Aronica, E., van Haastert, E. S., Hoozemans, J. J. M., Joels, M., & Lucassen, P. J. (2014) · Neural Plasticity · doi:10.1155/2014/693851 · Cited by 83 · cited 2× · see citing works
“…neuritic Aβ plaques and NFT in the temporal lobe, and increased microglial density and proliferation occurs concomitant with Aβ plaques and NFT in the hippocampus (Ekonomou et al., 2015; Harpin et al., 1990; Marlatt et al., 2014; McGeer et al., 1987; Simpson et al., 2010; Streit et al., 2009).”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain
Ciani, C., & Falcone, C. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1477753 · Cited by 11 · see citing works
- Authors
- Edler, M. K., Munger, E. L., Maycon, H., Hopkins, W. D., Hof, P. R., Sherwood, C. C., & Raghanti, M. A.
- Affiliations
- Kent State University (US)
- The University of Texas MD Anderson Cancer Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- George Washington University (US)
- Corresponding author
- Edler, Melissa K.
- ORCID
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2023-01-16
- Volume
- 101
- Issue
- 6
- Pages
- 881-900
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W4316927769
- Cited by
- 23
- References
- 13
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 7 · 2023: 1
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-01-09)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NIH 3U42OD011197‐19S1, NIH R01AG067419‐01A1, AG014308, NS092988)
- National Science Foundation of Sri Lanka (NSF BCS‐1846201)
- National Institute of Neurological Disorders and Stroke (NS0‐73134, NS‐402867)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- astrocyte activation, microglial activation, Alzheimer's disease, chimpanzees, brain aging, glial fibrillary acidic protein, dorsolateral prefrontal cortex, vascular amyloid, neuroinflammation, astrocyte density
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Brain, Pan troglodytes, Female, Gliosis, Humans, Male, Microglia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
