Volume 16, Number 10,
Issue of May 15, 1996
pp. 3311-3321
Copyright ©1996 Society for Neuroscience
Contingent Vulnerability of Entorhinal Parvalbumin-Containing
Neurons in Alzheimer's Disease
Received Sept. 25, 1995; revised Feb. 14, 1996; accepted Feb. 19, 1996.
Ana Solodkin1, 2,
Stacy D. Veldhuizen1, and
Gary W. Van Hoesen1, 2
Departments of 1 Anatomy and 2 Neurology,
University of Iowa, College of Medicine, Iowa City, Iowa 52242
Calcium-binding proteins containing local circuit neurons are
distributed ubiquitously in the human cerebral cortex where they
colocalize with a subpopulation of cells that contain GABA. Several
reports using a variety of pathological models, including Alzheimer's
disease (AD), have suggested that cells containing calcium-binding
proteins are resistant to pathological insults. In this report, we test
the hypothesis that AD pathology can differentially affect
parvalbumin-containing cells depending on their location in the
entorhinal cortex and the state of projection neurons with which they
are associated. Using cases with different quantities of AD pathology,
we determined the density of immunostaining for parvalbumin in the
entorhinal cortex, and we correlated this with the concomitant
pathological lesions in the various layers of this cortex.
Our results show a clear decrease in parvalbumin immunostaining in some
parts of the entorhinal cortex when AD neuropathological markers are
present. As the density of pathological markers in the entorhinal
cortex becomes greater and more widespread, there is a decrease of
parvalbumin immunostaining in additional layers, although in all cases,
some cells persist.
Parvalbumin-containing neurons are clearly vulnerable in AD, but not
because of neurofibrillary tangle formation. Instead, they are rendered
vulnerable only after substantial loss of projection neurons; only then
do they, too, become part of the lesion.
Key words:
parahippocampal gyrus;
calcium-binding proteins;
GABA;
Alzheimer's disease;
entorhinal cortex;
parvalbumin
immunohistochemistry