ApoE Lipidation as a Therapeutic Target in Alzheimer's Disease

• Published in: International journal of molecular sciences 2020-09, Vol.21 (17), p.6336
• Main Authors: Lanfranco, Maria Fe, Ng, Christi Anne, Rebeck, G William
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid; Animal models; Animals; Apolipoprotein E; Apolipoprotein E4; Apolipoproteins E - chemistry; Apolipoproteins E - metabolism; Brain; Central nervous system; Cholesterol; Genotype & phenotype; Health risk assessment; Homeostasis; Humans; Inflammation; Isoforms; Lipids; Lipids - chemistry; Neurodegeneration; Neuroprotection; Neuroprotective Agents - pharmacology; Physiology; Plasma; Proteins; Review; Risk analysis; Risk factors; Synaptogenesis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21176336

Apolipoprotein E ( ) is the major cholesterol carrier in the brain, affecting various normal cellular processes including neuronal growth, repair and remodeling of membranes, synaptogenesis, clearance and degradation of amyloid β (Aβ) and neuroinflammation. In humans, the gene has three common allelic variants, termed E2, E3, and E4. is considered the strongest genetic risk factor for Alzheimer's disease (AD), whereas is neuroprotective. To perform its normal functions, apoE must be secreted and properly lipidated, a process influenced by the structural differences associated with apoE isoforms. Here we highlight the importance of lipidated apoE as well as the -lipidation targeted therapeutic approaches that have the potential to correct or prevent neurodegeneration. Many of these approaches have been validated using diverse cellular and animal models. Overall, there is great potential to improve the lipidated state of apoE with the goal of ameliorating -associated central nervous system impairments.