Amyloidogenic role of cytokine TGF-β1 in transgenic mice and in Alzheimer's disease
Abstract
Deposition of amyoid-beta peptide in the central nervous system is a hallmark of Alzheimer's disease and a possible cause of neurodegeneration. The factors that initiate or promote deposition of amyloid-beta peptide are not known. The transforming growth factor TGF-beta1 plays a central role in the response of the brain to injury, and increased TGF-beta1 has been found in the central nervous system of patients with Alzheimer's disease. Here we report that TGF-beta1 induces amyloid-beta deposition in cerebral blood vessels and meninges of aged transgenic mice overexpressing this cytokine from astrocytes. Co-expression of TGF-beta1 in transgenic mice overexpressing amyloid-precursor protein, which develop Alzheimer's like pathology, accelerated the deposition of amyloid-beta peptide. More TGF-beta1 messenger RNA was present in post-mortem brain tissue of Alzheimer's patients than in controls, the levels correlating strongly with amyloid-beta deposition in the damaged cerebral blood vessels of patients with cerebral amyloid angiopathy. These results indicate that overexpression of TGF-beta1 may initiate or promote amyloidogenesis in Alzheimer's disease and in experimental models and so may be a risk factor for developing Alzheimer's disease.
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Overproduction of TGFβ in astrocytes promotes cerebrovascular fibrosis and amyloidosis.
“Although TGFβ signaling was suggested to play both beneficial and detrimental roles in AD 57 , its overproduction in astrocytes promotes cerebrovascular fibrosis and amyloidosis 58 .”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [58]
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- Authors
- Wyss-Coray, T., Masliah, E., Mallory, M., McConlogue, L., Johnson-Wood, K., Lin, C., & Mucke, L.
- Affiliations
- University of California San Diego (US)
- University of California, San Francisco (US)
- Venue
- Nature
- Published
- 1997-10
- Volume
- 389
- Issue
- 6651
- Pages
- 603-606
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1617304195
- Cited by
- 417
- References
- 2
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 12 · 2023: 11 · 2022: 13 · 2021: 6 · 2020: 12 · 2019: 9 · 2018: 8 · 2017: 7 · 2016: 14 · 2015: 7 · 2014: 17 · 2013: 16 · 2012: 12
- FWCI
- 15.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- TGF-β1, Alzheimer's disease, amyloid-beta deposition, amyloidogenesis, cerebral amyloid angiopathy, amyloid precursor protein, astrocytes, transgenic mice, cerebral vasculature, meninges, neurodegeneration, aging
- MeSH terms
- Aged, Aging, Alzheimer Disease, Amyloidosis, Animals, Astrocytes, Brain, Humans, Mice, Inbred BALB C, Mice, Transgenic, Thiazoles, Transforming Growth Factor beta, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Mice, Benzothiazoles
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