Striatal Expression of Glutamic Acid Decarboxylase Gene in Alzheimer's Disease

Abstract: To examine potential alteration of GABAergic striatal neurons in Alzheimer's disease, we used quantitative in situ hybridization to analyze the messenger RNA coding for M_r 67,000 glutamic acid decarboxylase (GAD₆₇ mRNA) in the striatum of five patients with Alzheimer's disease (AD) and nine matched control subjects. We found a 51–57% increase in the optical density of hybridization signal in the caudate nucleus and putamen, corresponding to a 30–42% increase in the number of neurons expressing a detectable amount of GAD₆₇ mRNA. By contrast, no alteration was observed in the ventral striatum. The expression of GAD₆₇ mRNA per neuron was similar in AD and control subjects both in the dorsal and ventral striatum. Taken together, our data indicate that, in AD, GABAergic neurotransmission is increased in the dorsal striatum but not in the ventral striatum. We suggest that this increased GABAergic neurotransmission may explain extrapyramidal signs often observed in AD.