title: Adjusting the compass: new insights into the role of angiogenesis in Alzheimer's disease.
abstract: Growing evidence suggests that vascular perturbation plays a critical role in the pathogenesis of Alzheimer's disease (AD). It appears to be a common feature in addition to the classic pathological hallmarks of amyloid beta (Aβ) plaques and neurofibrillary. Moreover, the accumulation of Aβ in the cerebral vasculature is closely associated with cognitive decline, and disruption of the blood-brain barrier (BBB) has been shown to coincide with the onset of cognitive impairment. Although it was originally hypothesized that the accumulation of Aβ and the subsequent disruption of the BBB were due to the impaired clearance of Aβ from the brain, a body of data now suggests an alternative hypothesis for vascular dysfunction in AD that amyloidogenesis promotes extensive neoangiogenesis leading to increased vascular permeability and subsequent hypervascularization. In this review, we discuss the role Aβ plays in angiogenesis of the neurovasculature and BBB and how it may contribute to the pathogenesis of AD. These studies suggest that interventions that directly or indirectly affect angiogenesis could have beneficial effects on amyloid and other pathways in AD.
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, 301-2185 East Mall, Vancouver, BC V6T 1Z4, Canada ; Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada ; The Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada ; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada ; Department of Zoology, University of British Columbia, 2370-6270 University Blvd, Vancouver, BC V6T 1Z4, Canada ; Department of Medical Genetics, 1364-2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: Jefferies
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA ; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Price
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, 301-2185 East Mall, Vancouver, BC V6T 1Z4, Canada ; Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada ; The Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.
authors.forename: Kaan E
authors.initials: KE
authors.lastname: Biron
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, 301-2185 East Mall, Vancouver, BC V6T 1Z4, Canada ; Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Franz
authors.initials: F
authors.lastname: Fenninger
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, 301-2185 East Mall, Vancouver, BC V6T 1Z4, Canada ; The Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.
authors.forename: Cheryl G
authors.initials: CG
authors.lastname: Pfeifer
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA ; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Dara L
authors.initials: DL
authors.lastname: Dickstein