2023
DOI: 10.1371/journal.pone.0281302
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Effects of sex and APOE ε4 genotype on brain mitochondrial high-energy phosphates in midlife individuals at risk for Alzheimer’s disease: A 31Phosphorus MR spectroscopy study

Abstract: Age, female sex, and APOE epsilon 4 (APOE4) genotype are the three greatest risk factors for late-onset Alzheimer’s disease (AD). The convergence of these risks creates a hypometabolic AD-risk profile unique to women, which may help explain their higher lifetime risk of AD. Less is known about APOE4 effects in men, although APOE4 positive men also experience an increased AD risk. This study uses 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) to examine effects of sex and APOE4 status on brain high-ener… Show more

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Cited by 7 publications
(14 citation statements)
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“…When considering HEP metabolite alterations during the normal aging process, the current literature suggests that PCr/ATP increases with age, though sex and genetic risk factors such as APOE4 influence the trajectory of these changes. Although results are not conclusive (Forester et al, 2010 ; Schmitz et al, 2018 ), PCr/ATP measures are lower in women compared to men independent of APOE4 status, and lower in male APOE4 carriers compared to non-carriers (Mosconi et al, 2021 ; Jett et al, 2022a , 2023 ). These findings are consistent with preclinical evidence of sex and APOE4 effects on brain mitochondrial deficits in animal models (Djordjevic et al, 2020 ), and translational studies of midlife individuals at risk for AD (Mosconi et al, 2017 , 2018a , b , 2021 ; Rahman et al, 2020 ).…”
Section: Discussionmentioning
confidence: 99%
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“…When considering HEP metabolite alterations during the normal aging process, the current literature suggests that PCr/ATP increases with age, though sex and genetic risk factors such as APOE4 influence the trajectory of these changes. Although results are not conclusive (Forester et al, 2010 ; Schmitz et al, 2018 ), PCr/ATP measures are lower in women compared to men independent of APOE4 status, and lower in male APOE4 carriers compared to non-carriers (Mosconi et al, 2021 ; Jett et al, 2022a , 2023 ). These findings are consistent with preclinical evidence of sex and APOE4 effects on brain mitochondrial deficits in animal models (Djordjevic et al, 2020 ), and translational studies of midlife individuals at risk for AD (Mosconi et al, 2017 , 2018a , b , 2021 ; Rahman et al, 2020 ).…”
Section: Discussionmentioning
confidence: 99%
“…These findings are also consistent with PET evidence for reduced CMRglc in cognitively normal midlife individuals at risk for AD (Mosconi et al, 2017 , 2018a , b , 2021 ; Shang et al, 2020 ). Additionally, a few recent 31 P-MRS studies indicate effects of endocrine aging in PCr/ATP levels among midlife women, with post-menopausal women exhibiting lower PCr/ATP as compared to age-controlled men as well as pre-menopausal controls, which have been interpreted as inability to meet energy requirements (Mosconi et al, 2021 ; Jett et al, 2022a , 2023 ). These findings are consistent with PET evidence of lower CMRglc in AD-vulnerable regions among post-menopausal women (Mosconi et al, 2018b , 2021 ), and provide further support to the notion that a triad of AD risk consisting of age, sex, and APOE4 genotype impacts bioenergetic pathways already in midlife (Riedel et al, 2016 ), further implicating the importance of mitochondrial alterations for AD risk (Riedel et al, 2016 ; Wang and Brinton, 2016 ).…”
Section: Discussionmentioning
confidence: 99%
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