Premorbid effects of APOE on synaptic proteins in human temporal neocortex

APOE affects the risk of Alzheimerʹs disease (AD) and course of several other neurologic diseases. Experimental studies suggest that APOE influences synaptogenesis. We measured the concentration of two presynaptic proteins, synaptophysin and syntaxin 1, and also postsynaptic density-95 (PSD95), in superior temporal cortex from 42 AD and 160 normal brains, and determined the APOE genotypes. The concentration of both presynaptic proteins was approximately two-thirds lower in AD than normal brains and that of PSD95 one-third lower. No effect of APOE on synaptic proteins was found in advanced AD. However, in normal brain, var epsilon4 was associated with lower concentrations of all three synaptic proteins and var epsilon2 with significantly elevated PSD95 (p = 0.03). A combined measure of synaptic proteins showed a significant linear decrease from var epsilon2 through var epsilon3 to var epsilon4 (p = 0.01). APOE influences the concentration of synaptic proteins in normal superior temporal cortex and may thereby affect the response to injury, and the risk and outcome of a range of neurologic diseases.