Contingent vulnerability of entorhinal parvalbumin-containing neurons in Alzheimer's disease.

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.