title: Progression of cerebral amyloid angiopathy in transgenic mouse models of Alzheimer disease.
abstract: Cerebral amyloid angiopathy (CAA), the deposition of beta-amyloid (Abeta3) in cerebral vessels, has been implicated as a common cause of hemorrhagic stroke and other forms of vascular disease. CAA is also a frequent concomitant of Alzheimer disease (AD). While the longterm consequences of CAA are well recognized from clinical and pathologic studies, numerous questions remain unanswered regarding the progression of the disease. Examination of CAA in traditional histologic sections does not easily allow for characterization of CAA, particularly in leptomeningeal vessels. In order to approach this topic, we used low magnification imaging of intact, postmortem brains from transgenic mouse models of AD-like pathology to define the spatial and temporal characteristics of CAA in leptomeningeal vessels. Imaging of brains from 10- to 26-month-old animals demonstrated a stereotypical pattern to the development of CAA, with vessels over the dorsal surface of the brain showing an anterior-to-posterior and large-to-small vessel gradient of involvement. High magnification imaging revealed that CAA deposition began with a banding pattern determined by the organization of the vascular smooth muscle cells. Further analysis of the pattern of amyloid deposits showed shrinkage and disappearance of the gaps between clusters of amyloid bands, gradually reaching a confluent pattern. These data led to a classification system to describe the severity of CAA deposition and demonstrate the potential of using intact brains to generate maps defining the progression and kinetics of CAA. This approach should lead to more informed analysis of the consequences of evolving therapeutic options for AD on this related form of vascular pathology.
authors.affiliation: Alzheimer Research Unit, Massachusetts General Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Domnitz
authors.forename: Elissa M
authors.initials: EM
authors.lastname: Robbins
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hoang
authors.forename: Monica
authors.initials: M
authors.lastname: Garcia-Alloza
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: G William
authors.initials: GW
authors.lastname: Rebeck
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bacskai
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology*; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D006801:Humans; D008578:Meninges / Q000098:blood supply / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016229:Amyloid beta-Peptides