Higher level of [3H]UCB-J binding in ApoE Ɛ4 allele carriers with Alzheimer disease

Neuronal and synapse losses are seen under the progression of Alzheimer's disease (AD). Accordingly, the binding to the synaptic vesicle glycoprotein 2A (SV2A) using the selective radioligand [3H]UCB-J was found to be reduced in frontal cortex from patients with AD. We report here that the reduction in SV2A binding is highly significant only in patients not carrying the ApoE ɛ4 allele. By contrast, those individuals with one or two ApoE ɛ4 alleles had SV2A binding levels not different from controls. Because ApoE4 is an important genetic risk and strongly linked to late-onset AD, this study raises an interesting new and unexpected association to SV2A, synapse loss, and function.