title: Cessation of neoangiogenesis in Alzheimer's disease follows amyloid-beta immunization.
abstract: Pathogenic neoangiogenesis in Alzheimer's disease (AD) is due to amyloid-beta (Aβ) and results in blood-brain barrier (BBB) leakiness in AD. It likely occurs as a compensatory response to impaired cerebral blood flow and provides a strong link between brain vascularity and AD. Aβ immunotherapy is an experimental treatment for AD; however, unexpected negative vascular side effects seen in early human clinical trials demonstrate that our knowledge of Aβ and AD pathogenesis is incomplete. We demonstrate that immunization with Aβ peptides neutralizes the amyloid trigger leading to neoangiogenesis and reverses hypervascularity in Tg2576 AD mice. This process resolves plaque burden suggesting that neoangiogenesis is a key mechanism underlying plaque formation. A meta-analysis demonstrated that hypervascular reversion in vaccinated Alzheimer's patients. This appears to be the first example of vascular reversion following any therapeutic intervention and supports the conclusion that modulation of neoangiogenesis may repair damage in the AD brain.
authors: Michael Smith Laboratories, The University of British Columbia, 301-2185 East Mall, Vancouver, British Columbia, V6T 1Z4, Canada.
authors: Kaan E
authors: KE
authors: Biron
authors: Dara L
authors: DL
authors: Dickstein
authors: Rayshad
authors: R
authors: Gopaul
authors: Franz
authors: F
authors: Fenninger
authors: Wilfred A
authors: WA
authors: Jefferies
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology*; D023582:Alzheimer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology; D001921:Brain / Q000098:blood supply; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology*; D019108:Tight Junctions / Q000473:pathology
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides