Deposition of amyloid-beta peptide in the central nervous system is a
hallmark of Alzheimer's disease and a possible cause of neurodegenerat
ion(1-3). The factors that initiate or promote deposition of amyloid-b
eta peptide are not known. The transforming growth factor TGF-beta 1 p
lays a central role in the response of the brain to injury(4,5), and i
ncreased TGF-beta 1 has been found in the central nervous system of pa
tients with Alzheimer's disease(6-8). Here we report that TGF-beta 1 i
nduces 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), acce
lerated the deposition of amyloid-beta peptide. More TGF-beta 1 messen
ger RNA was present in post-mortem brain tissue of Alzheimer's patient
s than in controls, the levels correlating strongly with amyloid-beta
deposition in the damaged cerebral blood vessels of patients with cere
bral amyloid angiopathy, These results indicate that overexpression of
TGF-beta 1 may initiate or promote amyloidogenesis in Alzheimer's dis
ease and in experimental models and so may be a risk factor for develo
ping Alzheimer's disease.