Cerebral Amyloid Angiopathy-Related Microhemorrhages in Alzheimer’s Disease: A Review of Investigative Animal Models

Abstract

There is a growing understanding of cerebral amyloid angiopathy (CAA), which accounts for the majority of primary lobal intracerebral hemorrhages (ICH) among the elderly [1] and is cited as the cause of 20% of spontaneous ICHs in patients over 70 years of age [2]. The basis for this disease process is the deposition and formation of eventually destructive amyloid plaques in the walls of brain vessels, predominantly arterial but not excluding venules and capillaries [3]. Investigation of the pathophysiology and therapies for CAA-associated hemorrhages have been made possible through animal models utilizing species that develop CAA in a similar fashion to humans, such as the squirrel monkey, rhesus monkey, dog and mutant and transgenic mouse strains, which exhibit the age-related development of amyloid plaques, progressive neurodegeneration and CAA-associated hemorrhages. The disease course in these animal models resembles that seen in the clinical setting for patients with CAA. Rodent studies have been able to demonstrate the strong role of CAA and CAA-associated microhemorrhages in the pathogenesis and progression of CAA with and without AD [4]. This review will present the existing understanding of CAA-associated microhemorrhages frequently observed in AD, different animal models, involved imaging and the role of animal models in the development of therapeutics including immunotherapies such as anti-Aβ antibodies for the treatment of CAA and its associated microhemorrhages.