Λεπτομέρειες βιβλιογραφικής εγγραφής
| Τίτλος: |
APOE Genotype-Stratified Meta-Analysis of Cognitive Decline Reveals Novel Loci for Language and Global Cognitive Function in Older Adults |
| Συγγραφείς: |
Vibha Acharya, Kang-Hsien Fan, Beth E. Snitz, Mary Ganguli, Steven T. DeKosky, Oscar L. Lopez, Eleanor Feingold, M. Ilyas Kamboh |
| Πηγή: |
International Journal of Molecular Sciences ; Volume 26 ; Issue 14 ; Pages: 6940 |
| Στοιχεία εκδότη: |
Multidisciplinary Digital Publishing Institute |
| Έτος έκδοσης: |
2025 |
| Συλλογή: |
MDPI Open Access Publishing |
| Θεματικοί όροι: |
APOE -stratified, genome-wide association, neurocognitive domains, attention, visuospatial function, memory, executive function, language, global cognitive function |
| Περιγραφή: |
Apolipoprotein E (APOE) allele 4 (APOE4), one of the robust genetic risk factors for AD, has also been associated with cognitive decline in terms of memory, executive function, language, and global cognitive function. APOE genotype-stratified analysis can help to identify additional genetic loci which might be masked due to a strong effect of APOE4. We conducted a genome-wide meta-analysis in APOE2 carriers, APOE4 carriers, and APOE 3/3 homozygote groups among 2969 non-Hispanic Whites aged ≥ 65 years using slopes of decline over time across five cognitive domains (attention, language, executive function, memory, and visuospatial function) and global cognitive function. We identified novel genome-wide significant associations for decline in global cognitive function in the intergenic region between RNU7-66P/RNA5SP208 at rs116379916 (p = 1.44 × 10−9) in the APOE 3/3 group and for decline in language in the intergenic region between LINC0221/DTWD2 at rs13187183 (p = 3.79 × 10−8) in APOE4 carriers. A previously reported locus for decline in attention near RASEF at rs6559700 (p = 9.95 × 10−9) was found to be confined to the APOE 3/3 group. We also found two sub-threshold significant associations in the APOE 2 group for decline in attention (IL1RL2/rs77127114; p = 8.64 × 10−8) and decline in language (YTHDC2/KCNN2, rs116191836; p = 5.66 × 10−8). Our study points to potential biological pathways pertaining to specific domains within each APOE genotype group, and the findings suggest that immune-related pathways, plasma levels of polysaturated fatty acids, and bitter taste receptors may play roles in cognitive decline. Our findings enhance the understanding of cognitive aging and provide a framework for future studies. |
| Τύπος εγγράφου: |
Thesis |
| Περιγραφή αρχείου: |
application/pdf |
| Γλώσσα: |
English |
| Relation: |
Molecular Genetics and Genomics; https://dx.doi.org/10.3390/ijms26146940 |
| DOI: |
10.3390/ijms26146940 |
| Διαθεσιμότητα: |
https://doi.org/10.3390/ijms26146940 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Αριθμός Καταχώρησης: |
edsbas.D1DDB9B2 |
| Βάση Δεδομένων: |
BASE |