Subsets of GABA Neurons in the Human Cerebellum in Normal Controls and Senile Dementia of the Alzheimer Type Patients Detected by Glutamate Decarboxylase, GABA<sub>A</sub>/Benzodiazepine Receptor Protein, Calbindin D-28k and Parvalbumin Immunocytochemistry (Part 1 of 2)

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The distribution of gamma-aminobutyric acid (GABA)-ergic neurons in the postmortem human cerebellar cortex and dentate nucleus was studied using antibodies against glutamate decarboxylase (GAD) and two different cytoplasmic calcium-binding proteins, parvalbumin and calbindin D-28k (CaBP), and the alpha-subunit of the GABA<sub>A</sub>/benzodiazepine receptor protein. The cerebellum of normal controls was compared to those of patients with senile dementia of the Alzheimer type (SDAT) in order to determine the involvement of these neurons in the dementing disorder. In the normal human cerebellar cortex all neuronal types except granule cells were GAD-labeled. Immunoreactivity was found predominantly in axonal structures, particularly in basket plexus around Purkinje cell somata. Antibodies against CaBP specifically stained all Purkinje cells in their entirety including axons and dendritic spines. Parvalbumin immunoreactivity was found in a subpopulation of Purkinje cells, basket and stellate cells but not in Golgi and granule cells. Parvalbumin-immunoreactive basket plexuses were found around Purkinje cell somata. The most intense labeling with the GABA<sub>A</sub>/benzodiazepine receptor antibody was found on the surface of granule cells. Purkinje, basket and stellate cells showed only a weak labeling of their surface. In the dentate nucleus only small neurons showed GAD immunoreactivity. Large neurons were densely covered with labeled axons and varicosities. No cell somata were stained with antibodies against CaBP and parvalbumin. All types of large and small dentate neurons showed immunoreactivity against GABA<sub>A</sub>/benzodiazepine receptor protein on the surface of their soma and dendrites. SDAT is accompanied by some changes in neurons belonging to the GABA subset. Fewer spines were found on the dendrites of Purkinje cells and on large dentate neurons. In the granular layer, more Purkinje axonal deformations ('torpedoes') and a hypertrophic network of Purkinje axon collaterals were found.