GenThADy · Gene therapeutic conversion from APOE4 to APOE3 to prevent Alzheimer’s disease

The major genetic risk factor for late-onset Alzheimer’s disease (AD) is the presence of the E4 allele of apolipoprotein E (APOE4). APOE is the primary lipid transporter in the brain, mainly expressed by astrocytes, microglia and neurons. There exist three APOE alleles in humans (E2, E3, E4). APOE4 increases the AD risk by 15-fold in homozygous and by 4-fold in heterozygous individuals. The APOE3 is not associated with increased risk and APOE2 is even associated with a reduced AD risk. Thus, new strategies to convert APOE4 into APOE3 represent a valid disease preventing treatment target for AD. Gene therapies are becoming more and more efficient and safe. To exploit this potential, we will develop a gene-therapy that converts APOE4 to APOE3 for the preventive treatment of AD.