Cerebral amyloid angiopathy (CAA), the deposition of cerebrovascular ?-amyloid (A?) in the walls of arterial vessels, has been impli-
to visualize in real time the initiation and progression of CAA in Tg2576 mice by multiphoton microscopy through cranial windows.
Affected vessels were labeled by methoxy-X04, a fluorescent dye that selectively binds cerebrovascular ?-amyloid and plaques. With
as well as appearance of new bands (additional initiation events). Statistical modeling of the data suggested that as the extent of CAA
ment, the overall pathology burden progressed at a rate of 0.35% of total available vessel area per day (95% confidence interval, 0.3–
There is increasing recognition of cerebrovascular disease as a
contributing factor to cognitive impairment and dementia
(O’Brien et al., 2003; Greenberg et al., 2004). Cerebral amyloid
cerebral arteries (and not veins), eventually resulting in smooth
muscle cell death (Mandybur, 1975; Vinters, 1987; Vonsattel et
al., 1991). CAA is often found in the presence of lobar hemor-
in these lesions in many people (Okazaki et al., 1979; Mandybur,
1986; Olichney et al., 1995; Cadavid et al., 2000). A?, which is
cleaved from the amyloid precursor protein (APP) and ranges
from 39 to 43 amino acids long, is also a key component of the
occur without evidence of AD, although it is more often associ-
CAA in humans in vivo and therefore little opportunity for un-
derstanding when or how CAA pathology develops. As new im-
aging agents are developed based on ability to bind A? in the
brain (Klunk et al., 2004), it may become possible to have a
presymptomatic measure of CAA pathology.
osition have played an important role in the understanding of
AD. Through the overexpression of forms of APP carrying AD-
or CAA-linked mutations, sometimes in combination with mu-
tations in presenilin-1, these animals generate high levels of A?
peptides. These animals develop A? deposits in the form of
plaques and represent a model of one component of the neuro-
pathology of AD (Games et al., 1995; Hsiao et al., 1996). In addi-
tion, many of these models develop CAA (Calhoun et al., 1999;
As with the human disease, these murine models of CAA are age
dependent (Domnitz et al., 2005), and the accumulation of A?
has deleterious effects including impaired reactivity (Iadecola et
al., 1999; Niwa et al., 2000; Christie et al., 2001a), microhemor-
muscle cells (Van Dorpe et al., 2000; Christie et al., 2001a; Win-
kler et al., 2001).
Although most previous studies of CAA in murine models
have focused on examination of histologic sections, that ap-
TheJournalofNeuroscience,January11,2006 • 26(2):365–371 • 365
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