APOE ε4 and exercise interact in a sex‐specific manner to modulate dementia risk factors
Abstract Introduction Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer's disease and related dementias (ADRDs), affecting many different pathways that lead to cognitive decline. Exercise is one of the most widely proposed prevention and intervention strategies to mi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/trc2.12308 |
| _version_ | 1826950809610354688 |
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| author | Kate E. Foley Cory A. Diemler Amanda A. Hewes Dylan T. Garceau Michael Sasner Gareth R. Howell |
| author_facet | Kate E. Foley Cory A. Diemler Amanda A. Hewes Dylan T. Garceau Michael Sasner Gareth R. Howell |
| author_sort | Kate E. Foley |
| collection | DOAJ |
| description | Abstract Introduction Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer's disease and related dementias (ADRDs), affecting many different pathways that lead to cognitive decline. Exercise is one of the most widely proposed prevention and intervention strategies to mitigate risk and symptomology of ADRDs. Importantly, exercise and APOE ε4 affect similar processes in the body and brain. While both APOE ε4 and exercise have been studied extensively, their interactive effects are not well understood. Methods To address this, male and female APOE ε3/ε3, APOE ε3/ε4, and APOE ε4/ε4 mice ran voluntarily from wean (1 month) to midlife (12 months). Longitudinal and cross‐sectional phenotyping were performed on the periphery and the brain, assessing markers of risk for dementia such as weight, body composition, circulating cholesterol composition, murine daily activities, energy expenditure, and cortical and hippocampal transcriptional profiling. Results Data revealed chronic running decreased age‐dependent weight gain, lean and fat mass, and serum low‐density lipoprotein concentration dependent on APOE genotype. Additionally, murine daily activities and energy expenditure were significantly influenced by an interaction between APOE genotype and running in both sexes. Transcriptional profiling of the cortex and hippocampus predicted that APOE genotype and running interact to affect numerous biological processes including vascular integrity, synaptic/neuronal health, cell motility, and mitochondrial metabolism, in a sex‐specific manner. Discussion These data in humanized mouse models provide compelling evidence that APOE genotype should be considered for population‐based strategies that incorporate exercise to prevent ADRDs and other APOE‐relevant diseases. |
| first_indexed | 2024-04-10T21:53:49Z |
| format | Article |
| id | doaj.art-dcd697927eed453f8598e777194b09ac |
| institution | Directory Open Access Journal |
| issn | 2352-8737 |
| language | English |
| last_indexed | 2025-02-17T22:37:39Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj.art-dcd697927eed453f8598e777194b09ac2024-12-03T12:37:31ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372022-01-0181n/an/a10.1002/trc2.12308APOE ε4 and exercise interact in a sex‐specific manner to modulate dementia risk factorsKate E. Foley0Cory A. Diemler1Amanda A. Hewes2Dylan T. Garceau3Michael Sasner4Gareth R. Howell5The Jackson Laboratory Bar Harbor Maine USAThe Jackson Laboratory Bar Harbor Maine USAThe Jackson Laboratory Bar Harbor Maine USAThe Jackson Laboratory Bar Harbor Maine USAThe Jackson Laboratory Bar Harbor Maine USAThe Jackson Laboratory Bar Harbor Maine USAAbstract Introduction Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer's disease and related dementias (ADRDs), affecting many different pathways that lead to cognitive decline. Exercise is one of the most widely proposed prevention and intervention strategies to mitigate risk and symptomology of ADRDs. Importantly, exercise and APOE ε4 affect similar processes in the body and brain. While both APOE ε4 and exercise have been studied extensively, their interactive effects are not well understood. Methods To address this, male and female APOE ε3/ε3, APOE ε3/ε4, and APOE ε4/ε4 mice ran voluntarily from wean (1 month) to midlife (12 months). Longitudinal and cross‐sectional phenotyping were performed on the periphery and the brain, assessing markers of risk for dementia such as weight, body composition, circulating cholesterol composition, murine daily activities, energy expenditure, and cortical and hippocampal transcriptional profiling. Results Data revealed chronic running decreased age‐dependent weight gain, lean and fat mass, and serum low‐density lipoprotein concentration dependent on APOE genotype. Additionally, murine daily activities and energy expenditure were significantly influenced by an interaction between APOE genotype and running in both sexes. Transcriptional profiling of the cortex and hippocampus predicted that APOE genotype and running interact to affect numerous biological processes including vascular integrity, synaptic/neuronal health, cell motility, and mitochondrial metabolism, in a sex‐specific manner. Discussion These data in humanized mouse models provide compelling evidence that APOE genotype should be considered for population‐based strategies that incorporate exercise to prevent ADRDs and other APOE‐relevant diseases.https://doi.org/10.1002/trc2.12308Alzheimer's diseaseapolipoprotein Edementiaexerciserunning |
| spellingShingle | Kate E. Foley Cory A. Diemler Amanda A. Hewes Dylan T. Garceau Michael Sasner Gareth R. Howell APOE ε4 and exercise interact in a sex‐specific manner to modulate dementia risk factors Alzheimer’s & Dementia: Translational Research & Clinical Interventions Alzheimer's disease apolipoprotein E dementia exercise running |
| title | APOE ε4 and exercise interact in a sex‐specific manner to modulate dementia risk factors |
| title_full | APOE ε4 and exercise interact in a sex‐specific manner to modulate dementia risk factors |
| title_fullStr | APOE ε4 and exercise interact in a sex‐specific manner to modulate dementia risk factors |
| title_full_unstemmed | APOE ε4 and exercise interact in a sex‐specific manner to modulate dementia risk factors |
| title_short | APOE ε4 and exercise interact in a sex‐specific manner to modulate dementia risk factors |
| title_sort | apoe ε4 and exercise interact in a sex specific manner to modulate dementia risk factors |
| topic | Alzheimer's disease apolipoprotein E dementia exercise running |
| url | https://doi.org/10.1002/trc2.12308 |
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