Amyloidogenic role of cytokine TGF-Beta-1 in transgenic mice and in Alzheimer's disease

Deposition of amyloid-β peptide in the central nervous system is a hallmark of Alzheimer's disease and a possible cause of neurodegeneration1,2,3. 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 injury4,5, and increased TGF-β1 has been found in the central nervous system of patients with Alzheimer's disease6,7,8. 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 pathology9,10,11, 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.