Effect of APOE genotype on synaptic proteins in earlier adult life

Background: Possession of APOE ϵ4 is a strong risk factor for late-onset Alzheimer's disease and is associated with loss of synaptic proteins in the elderly even in the absence of Alzheimer's disease. Objective: We hypothesized that ϵ4 allele possession in non-demented adults aged under-75 would also be associated with alterations in the levels of synaptic proteins. Methods: We measured synaptophysin, PSD95, drebrin, SNAP-25, and septin 7 by ELISA in hippocampus and superior temporal gyrus from 103 adults aged <75 without dementia. Corresponding gene expression was measured by RT-PCR. Results: There was no evidence that ϵ4 affected levels of the proteins measured. Instead we found an increase in post-synaptic proteins in the hippocampi of those with an ϵ32 genotype. The evidence was strongest for drebrin (p = 0.011). There was some evidence of increased synaptic protein gene expression in ϵ4 carriers. Conclusions: People with an APOE ϵ32 genotype have a reduced risk of Alzheimer's disease. It may be relevant that they have a higher level of post-synaptic proteins in the hippocampus even in earlier adulthood.