The <i>APOE</i> ε4 Allele Affects Cognitive Functions Differently in Carriers of <i>APP</i> Mutations Compared to Carriers of <i>PSEN1</i> Mutations in Autosomal-Dominant Alzheimer’s Disease
Mounting evidence shows that the <i>APOE</i> ε4 allele interferes with cognition in sporadic Alzheimer’s disease. Less is known about <i>APOE</i> in autosomal-dominant Alzheimer’s disease (adAD). The present study explored the effects on cognition associated with the gene–gen...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/12/12/1954 |
| _version_ | 1797504307142066176 |
|---|---|
| author | Ove Almkvist Caroline Graff |
| author_facet | Ove Almkvist Caroline Graff |
| author_sort | Ove Almkvist |
| collection | DOAJ |
| description | Mounting evidence shows that the <i>APOE</i> ε4 allele interferes with cognition in sporadic Alzheimer’s disease. Less is known about <i>APOE</i> in autosomal-dominant Alzheimer’s disease (adAD). The present study explored the effects on cognition associated with the gene–gene interactions between the <i>APOE</i> gene and the <i>APP</i> and <i>PSEN1</i> genes in adAD. This study includes mutation carriers (MC) and non-carriers (NC) from adAD families with mutations in <i>APP</i> (<i>n</i> = 28 and <i>n</i> = 25; MC and NC, respectively) and <i>PSEN1</i> (<i>n</i> = 12 and <i>n</i> = 15; MC and NC, respectively) that represent the complete spectrum of disease: AD dementia (<i>n</i> = 8) and mild cognitive impairment (MCI, <i>n</i> = 15 and presymptomatic AD, <i>n</i> = 17). NC represented unimpaired normal aging. There was no significant difference in the distribution of <i>APOE</i> ε4 (absence vs. presence) between the <i>APP</i> vs. <i>PSEN1</i> adAD genes and mutation status (MC vs. NC). However, episodic memory was significantly affected by the interaction between <i>APOE</i> and the <i>APP</i> vs. <i>PSEN1</i> genes in MC. This was explained by favorable performance in the absence of <i>APOE</i> ε4 in <i>PSEN1</i> compared to <i>APP</i> MC. Similar trends were seen in other cognitive functions. No significant associations between <i>APOE</i> ε4 and cognitive performance were obtained in NC. In conclusion, cognitive effects of <i>APOE</i>–adAD gene interaction were differentiated between the <i>PSEN1</i> and <i>APP</i> mutation carriers, indicating epistasis. |
| first_indexed | 2024-03-10T04:02:46Z |
| format | Article |
| id | doaj.art-c6a3efe0d2af476ca96d8a0af5d3ca08 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T04:02:46Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-c6a3efe0d2af476ca96d8a0af5d3ca082023-11-23T08:30:52ZengMDPI AGGenes2073-44252021-12-011212195410.3390/genes12121954The <i>APOE</i> ε4 Allele Affects Cognitive Functions Differently in Carriers of <i>APP</i> Mutations Compared to Carriers of <i>PSEN1</i> Mutations in Autosomal-Dominant Alzheimer’s DiseaseOve Almkvist0Caroline Graff1Division of Clinical Geriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet, SE-14157 Stockholm, SwedenTheme Aging, Karolinska University Hospital, SE-14157 Stockholm, SwedenMounting evidence shows that the <i>APOE</i> ε4 allele interferes with cognition in sporadic Alzheimer’s disease. Less is known about <i>APOE</i> in autosomal-dominant Alzheimer’s disease (adAD). The present study explored the effects on cognition associated with the gene–gene interactions between the <i>APOE</i> gene and the <i>APP</i> and <i>PSEN1</i> genes in adAD. This study includes mutation carriers (MC) and non-carriers (NC) from adAD families with mutations in <i>APP</i> (<i>n</i> = 28 and <i>n</i> = 25; MC and NC, respectively) and <i>PSEN1</i> (<i>n</i> = 12 and <i>n</i> = 15; MC and NC, respectively) that represent the complete spectrum of disease: AD dementia (<i>n</i> = 8) and mild cognitive impairment (MCI, <i>n</i> = 15 and presymptomatic AD, <i>n</i> = 17). NC represented unimpaired normal aging. There was no significant difference in the distribution of <i>APOE</i> ε4 (absence vs. presence) between the <i>APP</i> vs. <i>PSEN1</i> adAD genes and mutation status (MC vs. NC). However, episodic memory was significantly affected by the interaction between <i>APOE</i> and the <i>APP</i> vs. <i>PSEN1</i> genes in MC. This was explained by favorable performance in the absence of <i>APOE</i> ε4 in <i>PSEN1</i> compared to <i>APP</i> MC. Similar trends were seen in other cognitive functions. No significant associations between <i>APOE</i> ε4 and cognitive performance were obtained in NC. In conclusion, cognitive effects of <i>APOE</i>–adAD gene interaction were differentiated between the <i>PSEN1</i> and <i>APP</i> mutation carriers, indicating epistasis.https://www.mdpi.com/2073-4425/12/12/1954<i>APOE</i>autosomal-dominant Alzheimer’s disease<i>APP</i><i>PSEN1</i>cognitionepistasis |
| spellingShingle | Ove Almkvist Caroline Graff The <i>APOE</i> ε4 Allele Affects Cognitive Functions Differently in Carriers of <i>APP</i> Mutations Compared to Carriers of <i>PSEN1</i> Mutations in Autosomal-Dominant Alzheimer’s Disease Genes <i>APOE</i> autosomal-dominant Alzheimer’s disease <i>APP</i> <i>PSEN1</i> cognition epistasis |
| title | The <i>APOE</i> ε4 Allele Affects Cognitive Functions Differently in Carriers of <i>APP</i> Mutations Compared to Carriers of <i>PSEN1</i> Mutations in Autosomal-Dominant Alzheimer’s Disease |
| title_full | The <i>APOE</i> ε4 Allele Affects Cognitive Functions Differently in Carriers of <i>APP</i> Mutations Compared to Carriers of <i>PSEN1</i> Mutations in Autosomal-Dominant Alzheimer’s Disease |
| title_fullStr | The <i>APOE</i> ε4 Allele Affects Cognitive Functions Differently in Carriers of <i>APP</i> Mutations Compared to Carriers of <i>PSEN1</i> Mutations in Autosomal-Dominant Alzheimer’s Disease |
| title_full_unstemmed | The <i>APOE</i> ε4 Allele Affects Cognitive Functions Differently in Carriers of <i>APP</i> Mutations Compared to Carriers of <i>PSEN1</i> Mutations in Autosomal-Dominant Alzheimer’s Disease |
| title_short | The <i>APOE</i> ε4 Allele Affects Cognitive Functions Differently in Carriers of <i>APP</i> Mutations Compared to Carriers of <i>PSEN1</i> Mutations in Autosomal-Dominant Alzheimer’s Disease |
| title_sort | i apoe i ε4 allele affects cognitive functions differently in carriers of i app i mutations compared to carriers of i psen1 i mutations in autosomal dominant alzheimer s disease |
| topic | <i>APOE</i> autosomal-dominant Alzheimer’s disease <i>APP</i> <i>PSEN1</i> cognition epistasis |
| url | https://www.mdpi.com/2073-4425/12/12/1954 |
| work_keys_str_mv | AT ovealmkvist theiapoeie4alleleaffectscognitivefunctionsdifferentlyincarriersofiappimutationscomparedtocarriersofipsen1imutationsinautosomaldominantalzheimersdisease AT carolinegraff theiapoeie4alleleaffectscognitivefunctionsdifferentlyincarriersofiappimutationscomparedtocarriersofipsen1imutationsinautosomaldominantalzheimersdisease AT ovealmkvist iapoeie4alleleaffectscognitivefunctionsdifferentlyincarriersofiappimutationscomparedtocarriersofipsen1imutationsinautosomaldominantalzheimersdisease AT carolinegraff iapoeie4alleleaffectscognitivefunctionsdifferentlyincarriersofiappimutationscomparedtocarriersofipsen1imutationsinautosomaldominantalzheimersdisease |