Reduced cortical distribution volume of iodine-123 iomazenil in Alzheimer's disease as a measure of loss of synapses

Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABA(A) receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (V(d)) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends indiscriminately to affect all cortical neurons, albeit more so in some areas than in others. In this pilot study we measured V(d) in six patients with probable AD and in five age-matched controls using a brain-dedicated single-photon emission tomography scanner allowing all cortical levels to be sampled simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex V(d) was significantly (P < 0.02) reduced: temporal V(d) averaged 69 ml/ml in normals and 51 ml/ml in AD, and parietal V(d) averaged 71 ml/ml in normals and 48 ml/ml in AD, These results accord well with emission tomographic studies of blood flow or labelled glucose. This supports the idea that while only measuring a subpopulation of synapses, the IMZ method reflects synaptic loss and hence functional loss in AD. The method constitutes an in vivo version of synaptic quantitation that in histopathological studies has been shown to correlate closely with the mental deterioration in AD.