Targeting ApoE4/ApoE receptor LRP1 in Alzheimer's disease

Progressive neuronal loss is a key feature in Alzheimer's disease (AD), which is the most common neurodegenerative disorder in the aging population. Currently, there are no therapeutic means to intervene neuronal damage in AD and therefore innovative approaches to discover novel strategies for the treatment of AD are needed. Based on the prevailing amyloid cascade hypothesis, it is conceivable that lowering the β-amyloid (Aβ) levels is sufficient to slow down the disease process, if started early enough.

Here, we review genetic and biological functions related to apolipoprotein E (ApoE) and low-density lipoprotein receptor-related protein 1 receptor (LRP1)-mediated clearance of Aβ. Furthermore, we discuss the AD-related therapeutic potential of targeting to ApoE receptor LRP1 at the blood-brain barrier (BBB) and in the periphery.

Due to the recent setbacks in the clinical trials targeting AD, it is instrumental to seek alternative therapeutic approaches, which aim to reduce the accumulation of Aβ in the brain tissue. As the ApoE/LRP1-mediated clearance of Aβ across the BBB is the key event in the regulation of Aβ transcytosis from brain to periphery, direct targeting of this protein entity at the BBB holds a great potential in the treatment of AD.