DISTRIBUTION OF PARVALBUMIN-IMMUNOREACTIVE NEURONS IN BRAIN CORRELATES WITH HIPPOCAMPAL AND TEMPORAL CORTICAL PATHOLOGY IN CREUTZFELDT-JAKOB-DISEASE

There is a distinctive pattern of hippocampal involvement in Creutzfel dt-Jakob disease (CJD) and evidence for selective vulnerability of GAB Aergic neurons in experimental and human prion disease. We studied hip pocampus and temporal cortex from human CJD and control autopsy brains and surgical cryptogenic temporal lobe epilepsy specimens for distrib ution and density of parvalbumin (PV) and calbindin-D28K (Gal)-positiv e neurons that are subpopulations of GABAergic neurons. Pathology was evaluated semiquantitatively in 8 regions in 23 CJD brains for severit y of spongiform change, astrogliosis and pathological prion protein de position. In CJD, pathology was severe in pre-parasubiculum and tempor al cortex, and little or absent in CA1-4; PV+ neurons were severely re duced or absent in all cases, whereas Calf neurons were largely preser ved. In controls, the density of PV+ neurons was highest in pre-parasu biculum and temporal cortex, and lowest in CA1-4. In cTLE, loss of PV neurons was seen only in CA1-4. The diffuse and severe loss of PV+ ne urons in CJD, and the topographical correlation of tissue lesioning in CJD with density of PV+ neurons in controls suggest selective vulnera bility and early loss of this subset of inhibitory neurons in CJD. Thi s might relate to characteristic CJD symptoms such as myoclonus and th e distinctive EEG pattern.