Effect of APOE Genotype on Synaptic Proteins in Earlier Adult Life.

Possession of APOEɛ4 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. We hypothesized that ɛ4 allele possession in non-demented adults aged under-75 would also be associated with alterations in the levels of synaptic proteins. 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. There was no evidence that ɛ4 affected levels of the proteins measured. Instead we found an increase in post-synaptic proteins in the hippocampi of those with an ɛ32 genotype. The evidence was strongest for drebrin (p = 0.011). There was some evidence of increased synaptic protein gene expression in ɛ4 carriers. People with an APOEɛ32 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.