A serum protein signature of APOE genotypes in centenarians.
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ABSTRACT:
SUBMITTER: Sebastiani P
PROVIDER: S-EPMC6826130 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
A serum protein signature of APOE genotypes in centenarians.
Sebastiani Paola P Monti Stefano S Morris Melody M Gurinovich Anastasia A Toshiko Tanaka T Andersen Stacy L SL Sweigart Benjamin B Ferrucci Luigi L Jennings Lori L LL Glass David J DJ Perls Thomas T TT
Aging cell 20190805 6
The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late-onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e<sub>2</sub> allele of APOE has a neuroprotective effect, it is associated with increased longevity and an extended healthy lifespan in centenarians. In this study, we correlated APOE genotype data of 222 participants of the New England Centenarian S ...[more]
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Project description:Ages at natural menarche and menopause are influenced by several genetic factors. This study aimed to investigate the possible relationship between the apolipoprotein E (ApoE) genotype and the age at menarche and natural menopause in Chinese females. In the current study, 398 (elderly group, aged 47-80 years) and 825 (young group, aged 15-25 years) Chinese females were enrolled under informed content. Ages at natural menarche and menopause were obtained by questionnaires. ApoE genotypes were identified by restriction fragment length polymorphism analysis. In the elderly group, the number of pregnancies and live births and breastfeeding were associated with the age at menopause (P?=?0.008, P?=?0.002, and P?=?0.023, respectively). One-way ANOVA analysis revealed that the ApoE genotype was significantly associated with age at natural menopause (ANM; P?=?0.010). Compared with ApoE ?3/3 carriers, ApoE ?3/4 females showed a 1.8-year delay in ANM (P?=?0.002). Single ApoE allele-positive/allele-negative analysis also showed that the age at menopause of ApoE ?4 carriers was delayed compared with those who were not carriers (P?=?0.023). In the young group, no statistical difference was found in the age of menarche between the carriers of ApoE ?3/3 and ?3/4. Single ApoE allele-positive/allele-negative analysis showed that the age at menarche in ApoE ?4 carriers was slightly earlier than in those who were not carriers (P?=?0.048). Meanwhile, univariate association analysis revealed that the ApoE genotypes were not significantly associated with the age at menarche using age as a covariate in the pooled group (young?+?elderly) (P?=?0.143). We demonstrated that the ApoE genotype is significantly linked to the age at natural menopause.
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Project description:ObjectiveThe aims of the current study were to determine whether children with the 6 different APOE ε genotypes show differences in gray matter maturation, particularly for those with ε4 and ε2 alleles, which are associated with poorer outcomes in many neurologic disorders.MethodsA total of 1,187 healthy children (aged 3-20 years, 52.1% boys, 47.9% girls) with acceptable data from the cross-sectional Pediatric Imaging Neurocognition and Genetics Study were evaluated for the effects of 6 APOE ε genotypes on macroscopic and microscopic cortical and subcortical gray matter structures (measured with 3-tesla MRI and FreeSurfer for automated morphometry) and on cognition (NIH Toolbox).ResultsAmong APOE ε4 carriers, age-related changes in brain structures and cognition varied depending on genotype, with the smallest hippocampi in ε2ε4 children, the lowest hippocampal fractional anisotropy in younger ε4ε4 children, the largest medial orbitofrontal cortical areas in ε3ε4 children, and age-dependent thinning of the entorhinal cortex in ε4ε4 children. Younger ε4ε4 children had the lowest scores on executive function and working memory, while younger ε2ε4 children performed worse on attention tasks. Larger parietal gyri in the younger ε2ε4 children, and thinner temporal and cingulate isthmus cortices or smaller hippocampi in the younger ε4ε4 children, predicted poorer performance on attention or working memory.ConclusionsOur findings validated and extended prior smaller studies that showed altered brain development in APOE ε4-carrier children. The ε4ε4 and ε2ε4 genotypes may negatively influence brain development and brain aging at the extremes of age. Studying APOE ε polymorphisms in young children may provide the earliest indicators for individuals who might benefit from early interventions or preventive measures for future brain injuries and dementia.
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