Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease
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,...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.899644/full |
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| author | Jaya Bagaria Yeonsil Moon Eva Bagyinszky Kyu Hwan Shim Seong Soo A. An SangYun Kim Seol Heui Han |
| author_facet | Jaya Bagaria Yeonsil Moon Eva Bagyinszky Kyu Hwan Shim Seong Soo A. An SangYun Kim Seol Heui Han |
| author_sort | Jaya Bagaria |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-f0c7c590e9054ef49befd35cbb0cc6a3 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-12T18:10:39Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-f0c7c590e9054ef49befd35cbb0cc6a32022-12-22T03:21:50ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-06-011310.3389/fneur.2022.899644899644Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's DiseaseJaya Bagaria0Yeonsil Moon1Eva Bagyinszky2Kyu Hwan Shim3Seong Soo A. An4SangYun Kim5Seol Heui Han6Department of Bionanotechnology, Gachon University, Seongnam-si, South KoreaDepartment of Neurology, Konkuk University School of Medicine and Konkuk University Medical Center, Seoul, South KoreaDepartment of Industrial and Environmental Engineering, Graduate School of Environment, Gachon University, Seongnam, South KoreaDepartment of Bionanotechnology, Gachon University, Seongnam-si, South KoreaDepartment of Bionanotechnology, Gachon University, Seongnam-si, South KoreaDepartment of Neurology, Seoul National University College of Medicine and Seoul National University Budang Hospital, Seongnam-si, South KoreaDepartment of Neurology, Konkuk University School of Medicine and Konkuk University Medical Center, Seoul, South KoreaApolipoprotein (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.https://www.frontiersin.org/articles/10.3389/fneur.2022.899644/fullLow-Density Lipoprotein Receptor (LDLR)APOELeu159Proearly-onset Alzheimer's diseasenovel mutationWhole Exome Sequence (WES) analysis |
| spellingShingle | Jaya Bagaria Yeonsil Moon Eva Bagyinszky Kyu Hwan Shim Seong Soo A. An SangYun Kim Seol Heui Han Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease Frontiers in Neurology Low-Density Lipoprotein Receptor (LDLR) APOE Leu159Pro early-onset Alzheimer's disease novel mutation Whole Exome Sequence (WES) analysis |
| title | Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease |
| title_full | Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease |
| title_fullStr | Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease |
| title_full_unstemmed | Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease |
| title_short | Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease |
| title_sort | whole exome sequencing reveals a novel apoe mutation in a patient with sporadic early onset alzheimer s disease |
| topic | Low-Density Lipoprotein Receptor (LDLR) APOE Leu159Pro early-onset Alzheimer's disease novel mutation Whole Exome Sequence (WES) analysis |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.899644/full |
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