title: Amyloidogenic role of cytokine TGF-beta1 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.
authors.affiliation: Gladstone Molecular Neurobiology Program and Department of Neurology, University of California, San Francisco 94141-9100, USA. Tony_Wyss@quickmail.ucsf.edu
authors.forename: T
authors.initials: T
authors.lastname: Wyss-Coray
authors.forename: E
authors.initials: E
authors.lastname: Masliah
authors.forename: M
authors.initials: M
authors.lastname: Mallory
authors.forename: L
authors.initials: L
authors.lastname: McConlogue
authors.forename: K
authors.initials: K
authors.lastname: Johnson-Wood
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.forename: L
authors.initials: L
authors.lastname: Mucke
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013844:Thiazoles / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D013844:Thiazoles; D016212:Transforming Growth Factor beta; C009462:thioflavin T