100 research outputs found
Longer Leukocyte Telomere Length Is Associated with Smaller Hippocampal Volume among Non-Demented APOE ε3/ε3 Subjects
Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E ε4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 ε3/ε3 carriers; 28 ε4 carriers) aged 49–79 yr. Leukocyte telomere length correlated inversely with left (rs = −0.465; p = 0.011), right (rs = −0.414; p = 0.025), and total hippocampus volume (rs = −0.519; p = 0.004) among APOE ε3/ε3 carriers, but not among ε4 carriers. However, the ε4 carriers fit with the general correlation pattern exhibited by the ε3/ε3 carriers, as ε4 carriers on average had longer telomeres and smaller hippocampi compared with ε3/ε3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain
APOE ε4 lowers age at onset and is a high risk factor for Alzheimer's disease; A case control study from central Norway
<p>Abstract</p> <p>Background</p> <p>The objective of this study was to analyze factors influencing the risk and timing of Alzheimer's disease (AD) in central Norway. The <it>APOE </it>ε4 allele is the only consistently identified risk factor for late onset Alzheimer's disease (LOAD). We have described the allele frequencies of the apolipoprotein E gene (<it>APOE</it>) in a large population of patients with AD compared to the frequencies in a cognitively-normal control group, and estimated the effect of the <it>APOE </it>ε4 allele on the risk and the age at onset of AD in this population.</p> <p>Methods</p> <p>376 patients diagnosed with AD and 561 cognitively-normal control individuals with no known first degree relatives with dementia were genotyped for the <it>APOE </it>alleles. Allele frequencies and genotypes in patients and control individuals were compared. Odds Ratio for developing AD in different genotypes was calculated.</p> <p>Results</p> <p>Odds Ratio (OR) for developing AD was significantly increased in carriers of the <it>APOE </it>ε4 allele compared to individuals with the <it>APOE </it>ε3/ε3 genotype. Individuals carrying <it>APOE </it>ε4/ε4 had OR of 12.9 for developing AD, while carriers of <it>APOE </it>ε2/ε4 and <it>APOE </it>ε3/ε4 had OR of 3.2 and 4.2 respectively. The effect of the <it>APOE </it>ε4 allele was weaker with increasing age. Carrying the <it>APOE </it>ε2 allele showed no significant protective effect against AD and did not influence age at onset of the disease. Onset in LOAD patients was significantly reduced in a dose dependent manner from 78.4 years in patients without the <it>APOE </it>ε4 allele, to 75.3 in carriers of one <it>APOE </it>ε4 allele and 72.9 in carriers of two <it>APOE </it>ε4 alleles. Age at onset in early onset AD (EOAD) was not influenced by <it>APOE </it>ε4 alleles.</p> <p>Conclusion</p> <p><it>APOE </it>ε4 is a very strong risk factor for AD in the population of central Norway, and lowers age at onset of LOAD significantly.</p
A luteinizing hormone receptor intronic variant is significantly associated with decreased risk of Alzheimer's disease in males carrying an apolipoprotein E ε4 allele
Genetic and biochemical studies support the apolipoprotein E (APOE) ε4 allele as a major risk factor for late-onset Alzheimer's disease (AD), though ~50% of AD patients do not carry the allele. APOE transports cholesterol for luteinizing hormone (LH)-regulated steroidogenesis, and both LH and neurosteroids have been implicated in the etiology of AD. Since polymorphisms of LH beta-subunit (LHB) and its receptor (LHCGR) have not been tested for their association with AD, we scored AD and age-matched control samples for APOE genotype and 14 polymorphisms of LHB and LHCGR. Thirteen gene-gene interactions between the loci of LHB, LHCGR, and APOE were associated with AD. The most strongly supported of these interactions was between an LHCGR intronic polymorphism (rs4073366; lhcgr2) and APOE in males, which was detected using all three interaction analyses: linkage disequilibrium, multi-dimensionality reduction, and logistic regression. While the APOE ε4 allele carried significant risk of AD in males [p = 0.007, odds ratio (OR) = 3.08(95%confidence interval: 1.37, 6.91)], ε4-positive males carrying 1 or 2 C-alleles at lhcgr2 exhibited significantly decreased risk of AD [OR = 0.06(0.01, 0.38); p = 0.003]. This suggests that the lhcgr2 C-allele or a closely linked locus greatly reduces the risk of AD in males carrying an APOE ε4 allele. The reversal of risk embodied in this interaction powerfully supports the importance of considering the role gene-gene interactions play in the etiology of complex biological diseases and demonstrates the importance of using multiple analytic methods to detect well-supported gene-gene interactions
A randomized trial to reduce sugar-sweetened beverage and juice intake in preschool-aged children: description of the Smart Moms intervention trial
Abstract Background Obesity in young children remains a public health concern, and maternal weight is one of the strongest predictors of obesity in early childhood. However, parental adherence in interventions for young children is often low and existing programs have had mixed success. An innovative approach to treatment is needed that increases adherence among mothers and improves weight-related behaviors simultaneously in mothers and children. The objective of the Smart Moms randomized controlled trial (RCT) is to test the efficacy of a 6-month primarily smartphone-delivered program to reduce sugar-sweetened beverage and juice consumption among children ages 3–5 whose mothers are overweight or obese. This paper describes the study design and intervention. Methods/Design Mother-child dyads were eligible if the mother was overweight or obese, owned a smartphone, and if the child was between the ages of 3–5 and consumed 12 oz or more per day of sugar-sweetened beverages (SSBs) and 100 % fruit juice. Participants were randomly assigned to the Smart Moms intervention or a waitlist control group. The intervention consisted of theoretically grounded and evidence-based behavioral strategies delivered through one group session, lessons on a mobile-optimized website, and text messages. Mothers submitted self-monitoring information via text message and received regular tailored feedback emails from interventionists. The primary outcome is change in child SSB and juice consumption and a secondary outcome is change in maternal weight. Discussion This Smart Moms study was designed to determine if a low-burden intervention delivered using mobile methods and targeted towards mothers could be effective at changing child sugar-sweetened beverage intake. Results will indicate if mobile-based methods can be a feasible way to engage mothers in family-based studies and will inform successful strategies to prevent childhood obesity through parent-targeted approaches. Trial registration Clinicaltrials.gov NCT02098902 (Registered March 25, 2014)
Propagation of Tau aggregates.
Since 2009, evidence has accumulated to suggest that Tau aggregates form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of Tau aggregates is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighbouring cells. In mice, the intracerebral injection of Tau inclusions induced the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Short fibrils constituted the major species of seed-competent Tau. The existence of several human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist
“We’re Justchrw… Food and Perverse Entertainment”: Supernatural’s New God and the Narrative Objectification of Sam and Dean
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