| Title: |
Evaluating the association of apolipoprotein E genotype and cognitive resilience in SuperAgers |
| Authors: |
Durant, Alaina; Mukherjee, Shubhabrata; Lee, Michael L.; Choi, Seo-Eun; Scollard, Phoebe; Klinedinst, Brandon S.; Trittschuh, Emily H.; Mez, Jesse; Farrer, Lindsay A.; Gifford, Katherine A.; Cruchaga, Carlos; Hassenstab, Jason; Naj, Adam C.; Wang, Li-San; Johnson, Sterling C.; Engelman, Corinne D.; Kukull, Walter A.; Keene, C. Dirk; Saykin, Andrew J.; Cuccaro, Michael L.; Kunkle, Brian W.; Pericak-Vance, Margaret A.; Martin, Eden R.; Bennett, David A.; Barnes, Lisa L.; Schneider, Julie A.; Bush, William S.; Haines, Jonathan L.; Mayeux, Richard; Vardarajan, Badri N.; Albert, Marilyn S.; Thompson, Paul M.; Jefferson, Angela L.; Alzheimer's Disease Neuroimaging Initiative (ADNI); Alzheimer's Disease Genetics Consortium (ADGC); The Alzheimer's Disease Sequencing Project (ADSP); Crane, Paul K.; Dumitrescu, Logan; Archer, Derek B.; Hohman, Timothy J.; Gaynor, Leslie S. |
| Contributors: |
Radiology and Imaging Sciences, School of Medicine |
| Source: |
PMC |
| Publisher Information: |
Wiley |
| Publication Year: |
2026 |
| Collection: |
Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| Subject Terms: |
APOE genotype; Alzheimer's disease; SuperAgers; Cognitive aging; Cognitive resilience |
| Description: |
Introduction: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance more closely resembles middle-aged adults. The present study examined apolipoprotein E (APOE) allele frequency in non-Hispanic Black (NHB) and non-Hispanic White (NHW) SuperAgers compared to controls and Alzheimer's disease dementia cases. Methods: In 18,080 participants from eight cohorts, harmonized clinical diagnostics and memory, executive function, and language domain scores were used to identify SuperAgers, cases, and controls across age-defined bins. Results: NHW SuperAgers had significantly lower frequency of APOE-ε4 alleles and higher frequency of APOE-ε2 alleles compared to all cases and controls, including oldest-old controls. Similar patterns were found in a small yet substantial sample of NHB SuperAgers; however, not all comparisons with controls reached significance. Discussion: We demonstrated strong evidence that APOE allele frequency relates to SuperAger status. Further research is needed with a larger sample of NHB SuperAgers to determine if mechanisms conferring cognitive resilience differ across race groups. Highlights: Apolipoprotein E (APOE) allele frequency differs between SuperAgers and cases APOE allele frequency differs between non-Hispanic White SuperAgers and controls The relationship of APOE and non-Hispanic Black SuperAger status is unclear. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Alzheimer's & Dementia; Durant A, Mukherjee S, Lee ML, et al. Evaluating the association of apolipoprotein E genotype and cognitive resilience in SuperAgers. Alzheimers Dement. 2026;22(1):e71024. doi:10.1002/alz.71024; https://hdl.handle.net/1805/53894 |
| Availability: |
https://hdl.handle.net/1805/53894 |
| Rights: |
Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.885DE0FF |
| Database: |
BASE |