FUNCTIONAL ALTERATIONS IN ALZHEIMERS-DISEASE - DECREASED GLUCOSE-TRANSPORTER-3 IMMUNOREACTIVITY IN THE PERFORANT PATHWAY TERMINAL ZONE

Positron emission tomography (PET) studies measuring glucose utilizati on have demonstrated cerebral hypometabolism in Alzheimer's disease (A D). The anatomic and biochemical basis for this observation remains un known. We have examined the distribution in the hippocampal formation of the neuron-specific glucose transporter 3 (Glut3) protein. Using qu antitative immunohistochemistry, we find a large reduction (49.5%) in Glut3 immunoreactivity in the outer portion of the molecular layer of the dentate gyrus in AD brains. This region corresponds to the termina l zone of the perforant pathway, whose cells of origin in layer II of the entorhinal cortex are selectively destroyed in AD. Because glucose uptake reflects metabolic demand, these results suggest a decrement o f functional activity in the deafferented dentate gyrus granule cells. Generalizing from this observation, decreased glucose uptake seen on PET studies may reflect, in part, decreased glucose transport and util ization in functionally deafferented cortical fields.