Synaptic vesicle transport and synaptic membrane transporter sites in excitatory amino acid nerve terminals in Alzheimer disease

Abstract

The apparent l-[3H]glutamate uptake rate (v') was measured in synaptic vesicles isolated from cerebral cortex synaptosomes prepared from autopsied Alzheimer and non-Alzheimer dementia cases, and age-matched controls. The initial synaptosome preparations exhibited similar densities of d-[3H]aspartate membrane binding sites (BMAX values) in the three groups. In control brain the temporal cortex d-[3H]aspartate BMAX was 132% of that in motor cortex, parallel with the l-[3H]glutamate v' values (temporal=139% of motor; NS). Unlike d-[3H]aspartate BMAX values, l-[3H]glutamate v' values were markedly and selectively lower in Alzheimer brain preparations than in controls, particularly in temporal cortex. The difference could not be attributed to differential effects of autopsy interval or age at death. Non-Alzheimer dementia cases resembled controls. The selective loss of vesicular glutamate transport is consistent with a dysfunction in the recycling of transmitter glutamate.