Cerebral amyloid angiopathy (CAA) defines a biochemically heterogeneous entity that manifests as effacement of cerebral microvessel walls by a fibrillar material with characteristic tinctorial properties. In biochemical terms, the
amyloid that infiltrates blood vessels in CAA is composed of the A4 or beta
peptide of
Alzheimer's disease (AD), a molecule related to
gamma trace or
cystatin C (seen in patients with
hereditary cerebral hemorrhage with amyloidosis in Iceland,
HCHWA-I), or the PrP characteristic of spongiform
encephalopathy and
scrapie. Using
antibodies to synthetic
peptides representing portions of the 4.2-kd Alzheimer A4
peptide and the
gamma-trace peptide, we immunostained sections of brain from patients with AD,
senile dementia of Alzheimer's type, and CAA with associated
leukoencephalopathy. Immunohistochemical studies demonstrated colocalization of the A4 and
gamma-trace peptides within arteriolar walls, but only rarely in A4 amyloidotic capillaries or
senile plaque cores of
amyloid. When gamma-tracelike reactivity was noted in capillary walls, it was sometimes noted within the cytoplasm of pericytes. Immunostaining was always more intense when the anti-A4 antibody was used as the primary antibody.
Gamma-trace immunostaining was more prominent on the adventitial component of arteriolar walls, whereas A4 staining was usually seen more diffusely throughout the blood vessel wall, especially in the media. Rarely individual pericytelike cells showed prominent
gamma-trace immunoreactivity. These findings suggest that A4 and gamma-tracelike molecules may colocalize within arteriolar walls within the brains of patients with AD, and highlight the fact that CAA identified with AD and
HCHWA-I are not as biochemically distinct as was assumed previously. Furthermore these findings suggest that other
peptidases or
protease inhibitors may be found within amyloidotic microvessel walls and may contribute to senile brain change and CAA-related
strokes, including
hemorrhage and
encephalomalacia.