CONTINGENT VULNERABILITY OF ENTORHINAL PARVALBUMIN-CONTAINING NEURONSIN ALZHEIMERS-DISEASE

Calcium-binding proteins containing local circuit neurons are distribu ted ubiquitously in the human cerebral cortex where they colocalize wi th a subpopulation of cells that contain GABA. Several reports using a variety of pathological models, including Alzheimer's disease (AD), h ave suggested that cells containing calcium-binding proteins are resis tant to pathological insults. In this report, we test the hypothesis t hat AD pathology can differentially affect parvalbumin-containing cell s depending on their location in the entorhinal cortex and the state o f projection neurons with which they are associated. Using cases with different quantities of AD pathology, we determined the density of imm unostaining for panvalbumin in the entorhinal cortex, and we correlate d this with the concomitant pathological lesions in the various layers of this cortex. Our results show a clear decrease in parvalbumin immu nostaining in some parts of the entorhinal cortex when AD neuropatholo gical markers are present. As the density of pathological markers in t he entorhinal cortex becomes greater and more widespread, there is a d ecrease of parvalbumin immunostaining in additional layers, although i n all cases, some cells persist. Parvalbumin-containing neurons are cl early vulnerable in AD, but not because of neurofibrillary tangle form ation. Instead, they are rendered vulnerable only after substantial lo ss of projection neurons; only then do they, too, become part of the l esion.