Prevention and reduction of AD-type pathology in PDAPP mice immunized with A beta 1-42.
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.
Games
D
D
Elan Pharmaceuticals, 800 Gateway Blvd., So. San Francisco, CA 94080, USA. dgames@elanpharma.com
Bard
F
F
Grajeda
H
H
Guido
T
T
Khan
K
K
Soriano
F
F
Vasquez
N
N
Wehner
N
N
Johnson-Wood
K
K
Yednock
T
T
Seubert
P
P
Schenk
D
D
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*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)