Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease

• Published in: Frontiers in neurology Vol. 13; p. 899644
• Main Authors: Bagaria, Jaya, Moon, Yeonsil, Bagyinszky, Eva, Shim, Kyu Hwan, An, Seong Soo A., Kim, SangYun, Han, Seol Heui
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 10.06.2022
• Subjects: APOE; early-onset Alzheimer's disease; Leu159Pro; Low-Density Lipoprotein Receptor (LDLR); Neurology; novel mutation; Whole Exome Sequence (WES) analysis
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2022.899644

Apolipoprotein (APOE) is implicated and verified as the main risk factor for early-onset Alzheimer's disease (AD). APOE is a protein that binds to lipids and is involved in cholesterol stability. Our paper reports a case of a sporadic early-onset AD (sEOAD) patient of a 54-year-old Korean man, where a novel APOE Leu159Pro heterozygous mutation was revealed upon Whole Exome Sequence analysis. The proband's CSF showed downregulated levels of Aβ42, with unchanged Tau levels. The mutation is in the Low-Density Lipoprotein Receptor (LDLR) region of the APOE gene, which mediates the clearance of APOE lipoproteins. LDLR works as a high-affinity point for APOE. Studies suggest that APOE-LDLR interplay could have varying effects. The LDLR receptor pathway has been previously suggested as a therapeutic target to treat tauopathy. However, the APOE-LDLR interaction has also shown a significant correlation with memory retention. Leu159Pro could be an interesting mutation that could be responsible for a less damaging pattern of AD by suppressing tau-association neurodegeneration while affecting the patient's memory retention and cognitive performance.