By. Azizeh et al., Molecular dating of senile plaques in the drains of individuals with Down syndrome and in aged dogs, EXP NEUROL, 163(1), 2000, pp. 111-122
beta-Amyloid (A beta) is a constituent of senile plaques found with increas
ing age in individuals with Down syndrome (DS) and in the canine model of a
ging. Sections of DS and dog brain were immunostained using an affinity-pur
ified polyclonal antibody for a posttranslationally modified A beta with a
racemized aspartate at position 7 (d7C16). The immunostaining characteristi
cs of d7C16 A beta in DS and dog brain indicate that it is present in all p
laque subtypes, including the thioflavin-S-negative diffuse plaques that de
velop with age in dogs. The youngest DS case exhibited weak immunolabeling
for d7C16 but the extent of d7C16-positive plaques increased with age. In a
ddition, d7C16-positive plaques were initially found in clusters in the sup
erficial layers of the frontal and entorhinal cortex but, with advancing ag
e, increasing numbers appeared in deeper layers, suggesting a progression o
f A beta deposition from superficial to deeper cortical layers. Ultrastruct
ural studies in DS brain were confirmed using perfused dog brain and provid
ed consistent results; thioflavin-S-negative diffuse plaques consist of fib
rillar A beta and racemized A beta is associated with thicker and more high
ly interwoven fibrils than non-racemized A beta. The use of antibodies to m
odified forms of the A beta protein should provide insight into the progres
sion of plaque pathology in DS and Alzheimer's disease brain. (C) 2000 Acad
emic Press.