Effects of injected Alzheimer beta-amyloid cores in rat brain.
Open accessAbstract
Although amyloid deposits have long been known to accumulate in Alzheimer disease (AD) brain, their origin and significance remain speculative. Because of the lack of an in vivo model where amyloid deposits can be induced, the relationship of the extracellular beta-amyloid deposits to other AD pathology has never been directly investigated. Therefore, we injected SDS-isolated amyloid cores into rat cortex and hippocampus. Similarly isolated lipofuscin fractions from control human brains were injected on the contralateral side. Rats were perfused and brains were examined immunohistochemically at 2 days, 7 days, and 1 month after injection. Alz-50, a monoclonal antibody against abnormally phosphorylated tau proteins, stained neurons along the cortical needle track at 2 but not 7 days after injection of either amyloid or lipofuscin. At 1 month, however, ubiquitin, Alz-50 antigen, and silver-positive structures were observed only in response to amyloid. In 7 of 10 animals, there was considerable neuronal loss in the hippocampal layers. In each instance, these effects were in the immediate vicinity of beta-protein immunoreactive material. Marked neuronal loss was never observed at any time after lipofuscin injection. These results indicate a neuronal response to amyloid. When preparations of mature plaque amyloid isolated from the AD brain are injected into the rat brain, they exert neurotoxic effects and induce antigens found in the AD brain.
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Previous in vivo results range from showing that microglia are effective at phagocytosis of fibrillar amyloid to suggesting that microglia play no role in the control of amyloid deposition.
“Previous in vivo results range from showing that microglia are effective at phagocytosis of fibrillar amyloid (Frautschy et al., 1991; Bacskai et al., 2002; Bolmont et al., 2008) to suggesting that microglia play no role in the control of amyloid deposition (Grathwohl et al., 2009).”
From CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis (2010) · cites this paper as Frautschy et al., 1991
The indexed Abstract describes neuronal responses to amyloid cores injected into rat brain, but does not report microglial phagocytosis. Searches for microglia and phagocytosis returned only the abstract and references; the available indexed text does not establish the finding attributed to Frautschy et al. (LLM, conf=0.72)
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- Authors
- Frautschy, S. A., Baird, A., & Cole, G. M.
- Affiliations
- Scripps Whittier Diabetes Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1991-10
- Volume
- 88
- Issue
- 19
- Pages
- 8362-8366
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC52508
- OpenAlex
- W2038421461
- Cited by
- 254
- References
- 3
- Citations by year
- 2024: 6 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 9 · 2013: 9 · 2012: 7
- FWCI
- 12.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag009009-07)
- National Institute on Aging (AG-09009, R01AG010685)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 18811, P01DK018811)
- National Institute of Neurological Disorders and Stroke (NS 28121, P01NS028121)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, amyloid core, lipofuscin, neurotoxicity, neuronal loss, hippocampus, cortex, tau phosphorylation, ubiquitin, amyloid plaques
- MeSH terms
- Alzheimer Disease, Animals, Hippocampus, Humans, Infections, Lipofuscin, Time Factors, Amyloid beta-Peptides, Rats
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