Short-term memory advantage for brief durations in human APOE ε4 carriers
The Apolipoprotein-E (APOE) ε4 gene allele, the highest known genetic risk factor for Alzheimer’s disease, has paradoxically been well preserved in the human population. One possible explanation offered by evolutionary biology for survival of deleterious genes is antagonistic pleiotropy. This theory...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2020
|
| _version_ | 1797067572552663040 |
|---|---|
| author | Zokaei, N Grogan, J Fallon, SJ Slavkova, E Hadida, J Manohar, S De Ozorio Nobre, A Husain, M |
| author_facet | Zokaei, N Grogan, J Fallon, SJ Slavkova, E Hadida, J Manohar, S De Ozorio Nobre, A Husain, M |
| author_sort | Zokaei, N |
| collection | OXFORD |
| description | The Apolipoprotein-E (APOE) ε4 gene allele, the highest known genetic risk factor for Alzheimer’s disease, has paradoxically been well preserved in the human population. One possible explanation offered by evolutionary biology for survival of deleterious genes is antagonistic pleiotropy. This theory proposes that such genetic variants might confer an advantage, even earlier in life when humans are also reproductively fit. The results of some small-cohort studies have raised the possibility of such a pleiotropic effect for the ε4 allele in short-term memory (STM) but the findings have been inconsistent. Here, we tested STM performance in a large cohort of individuals (N = 1277); nine hundred and fifty-nine of which included carrier and non-carriers of the APOE ε4 gene, those at highest risk of developing Alzheimer’s disease. We first confirm that this task is sensitive to subtle deterioration in memory performance across ageing. Importantly, individuals carrying the APOE ε4 gene actually exhibited a significant memory advantage across all ages, specifically for brief retention periods but crucially not for longer durations. Together, these findings present the strongest evidence to date for a gene having an antagonistic pleiotropy effect on human cognitive function across a wide age range, and hence provide an explanation for the survival of the APOE ε4 allele in the gene pool. |
| first_indexed | 2024-03-06T21:58:15Z |
| format | Journal article |
| id | oxford-uuid:4db40e38-ac06-488d-8204-d18358b0a669 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:58:15Z |
| publishDate | 2020 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:4db40e38-ac06-488d-8204-d18358b0a6692022-03-26T15:56:50ZShort-term memory advantage for brief durations in human APOE ε4 carriersJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4db40e38-ac06-488d-8204-d18358b0a669EnglishSymplectic ElementsNature Research 2020Zokaei, NGrogan, JFallon, SJSlavkova, EHadida, JManohar, SDe Ozorio Nobre, AHusain, MThe Apolipoprotein-E (APOE) ε4 gene allele, the highest known genetic risk factor for Alzheimer’s disease, has paradoxically been well preserved in the human population. One possible explanation offered by evolutionary biology for survival of deleterious genes is antagonistic pleiotropy. This theory proposes that such genetic variants might confer an advantage, even earlier in life when humans are also reproductively fit. The results of some small-cohort studies have raised the possibility of such a pleiotropic effect for the ε4 allele in short-term memory (STM) but the findings have been inconsistent. Here, we tested STM performance in a large cohort of individuals (N = 1277); nine hundred and fifty-nine of which included carrier and non-carriers of the APOE ε4 gene, those at highest risk of developing Alzheimer’s disease. We first confirm that this task is sensitive to subtle deterioration in memory performance across ageing. Importantly, individuals carrying the APOE ε4 gene actually exhibited a significant memory advantage across all ages, specifically for brief retention periods but crucially not for longer durations. Together, these findings present the strongest evidence to date for a gene having an antagonistic pleiotropy effect on human cognitive function across a wide age range, and hence provide an explanation for the survival of the APOE ε4 allele in the gene pool. |
| spellingShingle | Zokaei, N Grogan, J Fallon, SJ Slavkova, E Hadida, J Manohar, S De Ozorio Nobre, A Husain, M Short-term memory advantage for brief durations in human APOE ε4 carriers |
| title | Short-term memory advantage for brief durations in human APOE ε4 carriers |
| title_full | Short-term memory advantage for brief durations in human APOE ε4 carriers |
| title_fullStr | Short-term memory advantage for brief durations in human APOE ε4 carriers |
| title_full_unstemmed | Short-term memory advantage for brief durations in human APOE ε4 carriers |
| title_short | Short-term memory advantage for brief durations in human APOE ε4 carriers |
| title_sort | short term memory advantage for brief durations in human apoe ε4 carriers |
| work_keys_str_mv | AT zokaein shorttermmemoryadvantageforbriefdurationsinhumanapoee4carriers AT groganj shorttermmemoryadvantageforbriefdurationsinhumanapoee4carriers AT fallonsj shorttermmemoryadvantageforbriefdurationsinhumanapoee4carriers AT slavkovae shorttermmemoryadvantageforbriefdurationsinhumanapoee4carriers AT hadidaj shorttermmemoryadvantageforbriefdurationsinhumanapoee4carriers AT manohars shorttermmemoryadvantageforbriefdurationsinhumanapoee4carriers AT deozorionobrea shorttermmemoryadvantageforbriefdurationsinhumanapoee4carriers AT husainm shorttermmemoryadvantageforbriefdurationsinhumanapoee4carriers |