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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




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