Apolipoprotein E in Alzheimer’s Disease

The pathophysiology of Alzheimer’s disease (AD) is related with the ongoing deterioration of brain lipid homeostasis, in which the cholesterol transporter apolipoprotein E (APOE) plays a key role. Plasma protein APOE might be additionally associated with AD due to its capability to bind the amyloid protein. There are three principal isoforms: APOE2, APOE3 and APOE4, encoded by three different alleles (ε2, ε3, ε4). Among them, APOE4 is recognized as the toxic form involved in AD development and progression. In fact, the presence of the ε4 allele correlates to an increase of about three times in the risk of developing the disease in late onset forms, both familiar and sporadic. For this reason, APOE4 has been often highlighted as a promising therapeutic target. Nevertheless, recent studies also suggest that the reduction of APOE protein levels, regardless of the isoform present, might be beneficial to deal with AD progression. Herein we report a brief overview of the proposed roles of APOE and in particular of ApoE4 in the insurgence and development of AD. In particular, its intervention in amyloid-β dependent and independent processes are examined. New therapeutic approaches for AD exploiting APOE as a target are finally discussed.