Testosterone modifies the effect of
 APOE
 genotype on hippocampal volume in middle-aged men

Panizzon, Matthew S.; Hauger, Richard L.; Dale, Anders M.; Eaves, Lindon J.; Eyler, Lisa T.; Fischl, Bruce; Fennema-Notestine, Christine; Franz, Carol E.; Grant, Michael D.; Jak, Amy J.; Jacobson, Kristen C.; Lyons, Michael J.; Mendoza, Sally P.; Neale, Michael C.; Prom‐Wormley, Elizabeth; Seidman, Larry J.; Tsuang, Ming T.; Xian, Hong; Kremen, William S.

doi:10.1212/wnl.0b013e3181f11deb

Cited by 42 publications

(33 citation statements)

References 38 publications

(35 reference statements)

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“…Protective effects of androgens against the deleterious effects of the APOE ε 4 allele have been documented in both male and female mice [Raber et al, 2002]. Paralleling the animal model findings, we found a significant interaction of APOE genotype and testosterone with respect to hippocampal volume [Panizzon et al, 2010]. Having at least one ε 4 allele was associated with smaller hippocampal volume, but only in the subgroup with low testosterone (defined as >1 SD below the mean).…”

Section: Apoesupporting

confidence: 80%

Genetics of brain structure: Contributions from the vietnam era twin study of aging

Kremen

Fennema-Notestine

Eyler

et al. 2013

American J of Med Genetics Pt B

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Understanding the genetics of neuropsychiatric disorders requires an understanding of the genetics of brain structure and function. The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study focused on cognitive and brain aging. Here, we describe basic science work carried out within the VETSA MRI study that provides meaningful contributions toward the study of neuropsychiatric disorders. VETSA produced the first comprehensive assessment of the heritability of cortical and subcortical brain structure sizes, all within the same individuals. We showed that neocortical thickness and surface area are largely genetically distinct. With continuous neocortical thickness maps, we demonstrated regional specificity of genetic influences, and that genetic factors did not conform to traditional regions of interest (ROIs). However, there was some evidence for different genetic factors accounting for different types of cortex, and for genetic relationships across cortical regions corresponding to anatomical and functional connectivity and brain maturation patterns. With continuous neocortical surface area maps, we confirmed the anterior–posterior gradient of genetic influences on cortical area patterning demonstrated in animal models. Finally, we used twin methods to create the first map of cortical ROIs based entirely on genetically informative data. We conclude that these genetically based cortical phenotypes may be more appropriate for genetic studies than traditional ROIs based on structure or function. Our results also suggest that cortical volume—the product of thickness and surface area is a problematic phenotype for genetic studies because two independent sets of genes may be obscured. Examples supporting the validity of these conclusions are provided.

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Section: Apoesupporting

confidence: 80%

Genetics of brain structure: Contributions from the vietnam era twin study of aging

Kremen

Fennema-Notestine

Eyler

et al. 2013

American J of Med Genetics Pt B

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“…On the other hand, in middle-aged men being ε4 allele carriers, the free testosterone level was positively associated with verbal episodic memory performance (story recall), whereas no association was observed in ε4 allele noncarriers [43]. Also individuals with both low free testosterone levels and at least one copy of the ε4 allele had smaller hippocampal volumes than men who had none or only one of these risk factors [44]. Interestingly, in a group of 816 Caucasian women, Fernández-Martínez et al [45] demonstrated that estrogen receptor polymorphisms are associated with mild cognitive impairment and AD in APOE ε4 carriers.…”

Section: Discussionmentioning

confidence: 99%

Cognitive Function, APOE Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Bojar¹,

Stasiak²,

Cyniak-Magierska³

et al. 2016

Dement Geriatr Cogn Disord

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Background: The objective of the study was to analyze a potential association between cognitive functions and thyroid status in postmenopausal women with different polymorphisms of the apolipoprotein E gene (APOE). Methods: The examined population included 402 postmenopausal women from south-eastern Poland. The evaluation of cognitive functions was made with the use of the diagnostic Central Nervous System-Vital Signs equipment (Polish version). Multiplex polymerase chain reactions were performed to assess APOE polymorphisms. The thyroid hormone tests were assessed by an accredited laboratory. Results and Conclusion: Lower results of cognitive functions were associated with the presence of the ε4 APOE allele in postmenopausal women. The ε4 APOE polymorphism was associated with a higher concentration of thyroid-stimulating hormone and lower concentrations of free triiodothyronine and total triiodothyronine.

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“…The ability of ApoE isoforms to promote Aβ clearance depends on the different lipidation status between them, as the higher lipidation promotes Aβ clearance [75], whereas ApoE-ε4 carriers have a lower level of lipidation and therefore a lower ability to clear Aβ deposition [76]. Testosterone levels influence the hippocampal volume in ApoE-ε4 allele carriers such that those with low testosterone and ApoE-ε4 carriers have the smallest hippocampal volumes [77]. Like females, males with AD also show higher levels of LH compared to the age-matched controls without AD [78]; however, males experience much more modest increases [79].…”

Section: Endocrinal Dysregulations In the Ad Pathophysiologymentioning

confidence: 99%

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

Ahmad

Fatima

Mondal³

2019

Neuropsychobiology

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Alzheimer’s disease (AD), the commonest progressive neurodegenerative disorder of the brain, is clinically characterized by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Recent studies suggest a relationship between the endocrinal dysregulation and the neuronal loss during the AD pathology. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis regulating circulating levels of glucocorticoid hormones has been implicated in the pathophysiology of AD. Likewise, dysregulated insulin signaling, impaired glucose uptake and insulin resistance are some of the prime factors in the onset/progression of AD. In this review, we have discussed the changes in HPA and HPG axes, implicated insulin resistance/signaling and glucose regulation during the onset/progression of AD. Therefore, simultaneous detection of these endocrinal markers in the early or presymptomatic stages may help in the early diagnosis of AD. This evidence for implicated endocrinal functions supports the fact that modulation of endocrinal pathways can be used as therapeutic targets for AD. Future studies need to determine how the induction or inhibition of endocrinal targets could be used for predictable neuroprotection in AD therapies.

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Testosterone modifies the effect of APOE genotype on hippocampal volume in middle-aged men

Abstract: Background:The APOE ⑀4 allele is an established risk factor for Alzheimer disease (AD), yet

Cited by 42 publications

References 38 publications

Genetics of brain structure: Contributions from the vietnam era twin study of aging

Genetics of brain structure: Contributions from the vietnam era twin study of aging

Cognitive Function, <b><i>APOE</i></b> Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

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