title: Prevention and reduction of AD-type pathology in PDAPP mice immunized with A beta 1-42.
abstract: In AD certain brain structures contain a pathological density of A beta protein deposited into plaques. The effect of genetic mutations found in early onset AD patients was an overproduction of A beta 42, strongly suggesting that overproduction of A beta 42 is associated with AD. We hypothesized that an immunological response to A beta 42 might alter its turnover and metabolism. Young PDAPP transgenic mice were immunized with A beta 1-42, which essentially prevented amyloid deposition; astrocytosis was dramatically reduced and there was reduction in A beta-induced inflammatory response as well. A beta 1-42 immunization also appeared to arrest the progression of amyloidosis in older PDAPP mice. A beta immunization appears to increase clearance of amyloid plaques, and may therefore be a novel and effective approach for the treatment of AD.
authors.affiliation: Elan Pharmaceuticals, 800 Gateway Blvd., So. San Francisco, CA 94080, USA. dgames@elanpharma.com
authors.forename: D
authors.initials: D
authors.lastname: Games
authors.forename: F
authors.initials: F
authors.lastname: Bard
authors.forename: H
authors.initials: H
authors.lastname: Grajeda
authors.forename: T
authors.initials: T
authors.lastname: Guido
authors.forename: K
authors.initials: K
authors.lastname: Khan
authors.forename: F
authors.initials: F
authors.lastname: Soriano
authors.forename: N
authors.initials: N
authors.lastname: Vasquez
authors.forename: N
authors.initials: N
authors.lastname: Wehner
authors.forename: K
authors.initials: K
authors.lastname: Johnson-Wood
authors.forename: T
authors.initials: T
authors.lastname: Yednock
authors.forename: P
authors.initials: P
authors.lastname: Seubert
authors.forename: D
authors.initials: D
authors.lastname: Schenk
mesh_terms: D000544:Alzheimer Disease / Q000382:microbiology / Q000473:pathology* / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism*; D000686:Amyloidosis / Q000517:prevention & control; D000818:Animals; D000917:Antibody Formation; D001253:Astrocytes / Q000473:pathology; D001921:Brain / Q000473:pathology; D005911:Gliosis; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)