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

Deposition of amyloid-beta peptide in the central nervous system is a hallmark of Alzheimer's disease and a possible cause of neurodegeneration(1-3). The factors that initiate or promote deposition of amyloid-beta peptide are not known. The transforming growth factor TGF-beta 1 plays a central role in the response of the brain to injury(4,5), and increased TGF-beta 1 has been found in the central nervous system of patients with Alzheimer's disease(6-8). Here we report that TGF-beta 1 induces amyloid-beta deposition in cerebral blood vessels and meninges of aged transgenic mice overexpressing this cytokine from astrocytes. Co-expression of TGF-beta 1 in transgenic mice overexpressing amyloid-precursor protein, which develop Alzheimer's like patholog(9-11), accelerated the deposition of amyloid-beta peptide. More TGF-beta 1 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-beta 1 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.