So far, the three-dimensional approach to senile plaques, one of the p
rincipal histopathological hallmarks in Alzheimer's disease besides ne
urofibrillary tangles, has been scarce. Two main problems in three-dim
ensional reconstruction of histological specimens are the horizontal d
istortion during the preparation of serial thin tissue-slides and the
need for consecutive Vertical readjustment. This is greatly facilitate
d by the reflection contrast microscope (Leica, Germany) which is a li
ght microscopical instrument causing interference patterns and reflect
ions along interfaces by means of circularly polarized epi-illuminatio
n. Using this technique, one can obtain distinct optical sections of a
depth of 1.5 mu m within specimens up to 30 mu m in thickness, thus p
reserving the integrity of the observed object and rendering a manual
alignment superfluous. We applied the reflection contrast microscope (
RCM) on thick tissue-slides of the cerebral cortex of a patient suffer
ing from Alzheimer's disease which had been dyed according to Campbell
. This is a silver-based staining method detecting beta A4-amyloid, th
e main component of senile plaques. Under the RCM, these silver-staine
d extracellular amyloid deposits cause reflections which allow the ass
essment of their three-dimensional distribution by focusing through th
e specimen. The optical sections obtained in this way were digitized,
and the identified senile plaques reconstructed by the grey-scale imag
e analysis system VIDAS 2.5 (Zeiss/Kontron, Germany).