Amyloidogenic role of cytokine TGF-β1 in transgenic mice and in Alzheimer's disease

• Published in: Nature (London) Vol. 389; no. 6651; pp. 603 - 606
• Main Authors: Wyss-Coray, Tony, Masliah, Eliezer, Mallory, Margaret, McConlogue, Lisa, Johnson-Wood, Kelly, Lin, Carol, Mucke, Lennart
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.10.1997
• Subjects: Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Medical sciences; Neurology; Animal model; Meninge; Nervous system diseases; Alzheimer disease; Transforming growth factor β; Pathogenesis; Rodentia; Central nervous system; Transgenic animal; Cerebral disorder; Vertebrata; Mammalia; Mouse; β Amyloid protein; Blood vessel; Central nervous system disease; Degenerative disease; Circulatory system; Brain (vertebrata)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/39321

Deposition of amyloid-β 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-β peptide are not known. The transforming growth factor TGF-β1 plays a central role in the response of the brain to injury,, and increased TGF-β1 has been found in the central nervous system of patients with Alzheimer's disease. Here we report that TGF-β1 induces amyloid-β deposition in cerebral blood vessels and meninges of aged transgenic mice overexpressing this cytokine from astrocytes. Co-expression of TGF-β1 in transgenic mice overexpressing amyloid-precursor protein, which develop Alzheimer's like pathology, accelerated the deposition of amyloid-β peptide. More TGF-β1 messenger RNA was present in post-mortem brain tissue of Alzheimer's patients than in controls, the levels correlating strongly with amyloid-β deposition in the damaged cerebral blood vessels of patients with cerebral amyloid angiopathy. These results indicate that overexpression of TGF-β1 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.