Interaction between <i>KLOTHO</i>-VS Heterozygosity and <i>APOE</i> ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s Disease
<i>KLOTHO</i>-VS heterozygosity (<i>KL</i>-VS<sup>het+</sup>) promotes longevity and protects against cognitive decline in aging. To determine whether <i>KL</i>-VS<sup>het+</sup> mitigates Alzheimer’s disease (AD) progression, we used longi...
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MDPI AG
2023-04-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/4/917 |
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| author | Xi Richard Chen Yongzhao Shao Martin J. Sadowski on behalf of the Alzheimer’s Disease Neuroimaging Initiative |
| author_facet | Xi Richard Chen Yongzhao Shao Martin J. Sadowski on behalf of the Alzheimer’s Disease Neuroimaging Initiative |
| author_sort | Xi Richard Chen |
| collection | DOAJ |
| description | <i>KLOTHO</i>-VS heterozygosity (<i>KL</i>-VS<sup>het+</sup>) promotes longevity and protects against cognitive decline in aging. To determine whether <i>KL</i>-VS<sup>het+</sup> mitigates Alzheimer’s disease (AD) progression, we used longitudinal linear-mixed models to compare the rate of change in multiple cognitive measures in AD patients stratified by <i>APOE ε4</i> carrier status. We aggregated data on 665 participants (208 <i>KL</i>-VS<sup>het−</sup>/<i>ε4−</i>, 307 <i>KL</i>-VS<sup>het−</sup>/<i>ε4+</i>, 66 <i>KL</i>-VS<sup>het+</sup>/<i>ε4−</i>, and 84 <i>KL</i>-VS<sup>het+</sup>/<i>ε4+</i>) from two prospective cohorts, the National Alzheimer’s Coordinating Center and the Alzheimer’s Disease Neuroimaging Initiative. All participants were initially diagnosed with mild cognitive impairment, later developed AD dementia during the study, and had at least three subsequent visits. <i>KL</i>-VS<sup>het+</sup> conferred slower cognitive decline in <i>ε4</i> non-carriers (+0.287 MMSE points/year, <i>p</i> = 0.001; −0.104 CDR-SB points/year, <i>p</i> = 0.026; −0.042 ADCOMS points/year, <i>p</i> < 0.001) but not in <i>ε4</i> carriers who generally had faster rates of decline than non-carriers. Stratified analyses showed that the protective effect of <i>KL</i>-VS<sup>het+</sup> was particularly prominent in male participants, those who were older than the median baseline age of 76 years, or those who had an education level of at least 16 years. For the first time, our study provides evidence that <i>KL</i>-VS<sup>het+</sup> status has a protective effect on AD progression and interacts with the <i>ε4</i> allele. |
| first_indexed | 2024-03-11T04:59:19Z |
| format | Article |
| id | doaj.art-b5682217e1a84bc891ac94bcacb85c54 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T04:59:19Z |
| publishDate | 2023-04-01 |
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| record_format | Article |
| series | Genes |
| spelling | doaj.art-b5682217e1a84bc891ac94bcacb85c542023-11-17T19:24:25ZengMDPI AGGenes2073-44252023-04-0114491710.3390/genes14040917Interaction between <i>KLOTHO</i>-VS Heterozygosity and <i>APOE</i> ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s DiseaseXi Richard Chen0Yongzhao Shao1Martin J. Sadowski2on behalf of the Alzheimer’s Disease Neuroimaging InitiativeSchool of Medicine & Dentistry, University of Rochester, Rochester, NY 14642, USADepartment of Population Health, NYU Grossman School of Medicine, New York, NY 10016, USADepartment of Neurology, NYU Grossman School of Medicine, New York, NY 10016, USA<i>KLOTHO</i>-VS heterozygosity (<i>KL</i>-VS<sup>het+</sup>) promotes longevity and protects against cognitive decline in aging. To determine whether <i>KL</i>-VS<sup>het+</sup> mitigates Alzheimer’s disease (AD) progression, we used longitudinal linear-mixed models to compare the rate of change in multiple cognitive measures in AD patients stratified by <i>APOE ε4</i> carrier status. We aggregated data on 665 participants (208 <i>KL</i>-VS<sup>het−</sup>/<i>ε4−</i>, 307 <i>KL</i>-VS<sup>het−</sup>/<i>ε4+</i>, 66 <i>KL</i>-VS<sup>het+</sup>/<i>ε4−</i>, and 84 <i>KL</i>-VS<sup>het+</sup>/<i>ε4+</i>) from two prospective cohorts, the National Alzheimer’s Coordinating Center and the Alzheimer’s Disease Neuroimaging Initiative. All participants were initially diagnosed with mild cognitive impairment, later developed AD dementia during the study, and had at least three subsequent visits. <i>KL</i>-VS<sup>het+</sup> conferred slower cognitive decline in <i>ε4</i> non-carriers (+0.287 MMSE points/year, <i>p</i> = 0.001; −0.104 CDR-SB points/year, <i>p</i> = 0.026; −0.042 ADCOMS points/year, <i>p</i> < 0.001) but not in <i>ε4</i> carriers who generally had faster rates of decline than non-carriers. Stratified analyses showed that the protective effect of <i>KL</i>-VS<sup>het+</sup> was particularly prominent in male participants, those who were older than the median baseline age of 76 years, or those who had an education level of at least 16 years. For the first time, our study provides evidence that <i>KL</i>-VS<sup>het+</sup> status has a protective effect on AD progression and interacts with the <i>ε4</i> allele.https://www.mdpi.com/2073-4425/14/4/917Alzheimer’s disease<i>KLOTHO</i><i>APOE</i>cognitive declineaging |
| spellingShingle | Xi Richard Chen Yongzhao Shao Martin J. Sadowski on behalf of the Alzheimer’s Disease Neuroimaging Initiative Interaction between <i>KLOTHO</i>-VS Heterozygosity and <i>APOE</i> ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s Disease Genes Alzheimer’s disease <i>KLOTHO</i> <i>APOE</i> cognitive decline aging |
| title | Interaction between <i>KLOTHO</i>-VS Heterozygosity and <i>APOE</i> ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s Disease |
| title_full | Interaction between <i>KLOTHO</i>-VS Heterozygosity and <i>APOE</i> ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s Disease |
| title_fullStr | Interaction between <i>KLOTHO</i>-VS Heterozygosity and <i>APOE</i> ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s Disease |
| title_full_unstemmed | Interaction between <i>KLOTHO</i>-VS Heterozygosity and <i>APOE</i> ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s Disease |
| title_short | Interaction between <i>KLOTHO</i>-VS Heterozygosity and <i>APOE</i> ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s Disease |
| title_sort | interaction between i klotho i vs heterozygosity and i apoe i ε4 allele predicts rate of cognitive decline in late onset alzheimer s disease |
| topic | Alzheimer’s disease <i>KLOTHO</i> <i>APOE</i> cognitive decline aging |
| url | https://www.mdpi.com/2073-4425/14/4/917 |
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