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Leon et al. Neuroimmunol Neuroinflammation 2018;5:30 Neuroimmunology and
DOI: 10.20517/2347-8659.2018.26 Neuroinflammation

Review Open Access

Therapeutic approach targeting apolipoprotein E
binding region and low-density lipoprotein receptor
for Alzheimer’s disease

Michael Leon , Darrell Sawmiller , Brian Giunta , Jun Tan 1
1
1
2
1 Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral
Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL 33613, USA.
2 Neuroimmunology Laboratory, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of
South Florida, Tampa, FL 33613, USA.
Correspondence to: Dr. Michael Leon, Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center,
Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, 3515 E Fletcher
Ave, Tampa, FL 33613, USA. E-mail: mleon@health.usf.edu
How to cite this article: Leon M, Sawmiller D, Giunta B, Tan J. Therapeutic approach targeting apolipoprotein E binding region and
low-density lipoprotein receptor for Alzheimer’s disease. Neuroimmunol Neuroinflammation 2018;5:30.
http://dx.doi.org/10.20517/2347-8659.2018.26

Received: 8 May 2018 First Decision: 11 Jun 2018 Revised: 19 Jul 2018 Accepted: 20 Jul 2018 Published: 31 Jul 2018
Science Editor: Athanassios P. Kyritsis Copy Editor: Jun-Yao Li Production Editor: Huan-Liang Wu

ABSTRACT
Approximately 13% of the population over the age of 65 years is estimated to have AD. The total number of cases is
expected to increase over the coming decades. The apolipoprotein E (ApoE) genotype is the greatest genetic deter-
minant for Alzheimer’s disease (AD) development. The ApoE4 allele increases the risk of AD by 4 to 14 fold while
the ApoE2 allele has an opposing effect; decreasing risk. Indeed many studies have demonstrated that carriers of
the ApoE2 allele are associated with greater likelihood of survival to advanced age, superior verbal learning ability in
advanced age, and reduced accumulation of amyloid pathology in the aged brain. In addition, it is known that ApoE
proteins have different affinities for the low-density lipoprotein receptor (LDLR), with ApoE2 having the weakest
binding to the LDL receptor at < 2% relative to ApoE3 and E4. Because ApoE2 has shown protective effects in re-
gard to AD, a novel approach for ApoE4 carriers may be to create a peptide antagonist that blocks the ApoE inter-
actions with LDLR at its 135-150 N-terminal binding domain. This peptide may create a more ApoE2-like structure
by decreasing the affinity of ApoE4 for LDLR thereby reducing AD onset, memory impairment, and amyloid plaque
formation. In this review, we will discuss the different detrimental effects that ApoE4 can cause. Most importantly,
we will review how ApoE4 binding to LDLR promotes AD pathogenesis and how blocking ApoE4 binding may be a
promising novel therapeutic approach for AD.

Keywords: Alzheimer’s disease, low-density lipoprotein receptor, apolipoprotein E, amyloid precursor protein, late
onset Alzheimer’s disease
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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