Publication: Cerebral ß-amyloid angiopathy in aged squirrel monkeys
Authors
Elfenbein, H.A. ; Rosen, R.F. ; Stephens, S.L. ; Switzer, R.C. ; Smith, Y. ; Pare, J. ; Mehta, P.D. ; Warzok, R. ; Walker, L.C.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Cerebral ß-amyloid angiopathy (CAA) is an
age-related disorder of the brain vasculature that is
involved in up to 20% of non-traumatic cerebral
hemorrhage in humans. CAA is a risk factor for
cognitive decline, and may exacerbate the dementia of
Alzheimer's disease. Progress in discovering the cause
and potential therapies for this disorder has been
hindered by the paucity of animal models, particularly
models of idiopathic CAA. The squirrel monkey
(Saimiri spp) develops significant CAA in the natural
course of aging. To evaluate the suitability of Saimiri as
a model of human CAA, we studied the distribution and
composition of Aß subtypes in CAA and parenchymal
(senile plaque) deposits in the brains of aged squirrel
monkeys, as well as the relationship between vascular ßamyloid
deposition and comorbid vasculopathies that
occur in aged humans. Our findings show that: 1) CAA
consists ultrastructurally of classical amyloid fibrils and is the principal type of cerebral ß-amyloidosis in squirrel
monkeys; 2) The two primary isoforms of Aß (Aß40 and
Aß42) coexist in most microvascular and parenchymal
lesions of Saimiri, although Aß40 tends to predominate
in larger arterioles; 3) CAA and parenchymal plaques
overlap to a considerable degree in most affected brain
areas, and are distributed symmetrically in the two
hemispheres; 4) Both CAA and plaques are particularly
abundant in rostral regions and comparatively sparse in
the occipital lobe; 5) Capillaries are especially
vulnerable to CAA in squirrel monkeys; and 6) When
CAA is severe, it is associated with a small, but
significant, increase in other vasculopathies, including
microhemorrhage, fibrinoid extravasation and focal
gliosis. These findings, in the context of genetic,
vascular and immunologic similarities between squirrel
monkeys and humans, support the squirrel monkey as a
biologically advantageous model for studying the basic
biology of idiopathic, age-related CAA, and for testing emerging therapies for human ß-amyloidoses such as
Alzheimer's disease.
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