APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory

Wikgren, Mikael; Karlsson, Thomas; Nilbrink, Therese; Nordfjäll, Katarina; Hultdin, Johan; Sleegers, Kristel; Broeckhoven, Christine Van; Nyberg, Lars; Roos, Göran; Nilsson, Lars‐Göran; Adolfsson, Rolf; Norrbäck, Karl-Fredrik

doi:10.1016/j.neurobiolaging.2010.03.004

Cited by 44 publications

(39 citation statements)

References 43 publications

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“…Also, telomeres may be interacting with other genetic determinants to influence brain size. We did not find herein that the associations between brain volumes and telomere length were substantially altered after adjusting for APOE genotype, which has been previously linked to telomere length 36,46 and Alzheimer disease risk. 47 Because telomere length mirrors endogenous telomerase activity, leukocyte telomere length may also be a surrogate marker of brain cell proliferation potential.…”

Section: Discussioncontrasting

confidence: 66%

Effect of Leukocyte Telomere Length on Total and Regional Brain Volumes in a Large Population-Based Cohort

et al. 2014

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Section: Discussioncontrasting

confidence: 66%

Effect of Leukocyte Telomere Length on Total and Regional Brain Volumes in a Large Population-Based Cohort

et al. 2014

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“…One study found an inverse association of telomere length with age and longer telomere lengths in men than in women (Honig et al, 2012). We did not find interactions of telomere length with APOE ε4 carrier status in regard to risk of aMCI as some investigators have reported for other cognitive endpoints (Honig et al, 2006; Wikgren et al, 2012a; Wikgren et al, 2012b; Yaffe et al, 2011). …”

Section: Discussioncontrasting

confidence: 52%

“…Consistent with our findings, other investigators have not observed sex differences in telomere length (Hochstrasser et al, 2012; Zekry et al, 2010b). Some studies among middle aged subjects, however, have demonstrated longer telomere lengths in adult women (Adams et al, 2007; Aviv et al, 2005; Bischoff et al, 2005; Bischoff et al, 2006; Der et al, 2012; Nordfjall et al, 2010; Wikgren et al, 2012b; Yaffe et al, 2011). One study found an inverse association of telomere length with age and longer telomere lengths in men than in women (Honig et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…The increased risk of aMCI with longer telomere length is consistent with a study among persons from a memory clinic which reported that MCI cases who progressed to dementia had significantly longer telomere lengths compared to stable MCI (Moverare-Skrtic et al, 2012). Two cross-sectional studies reported associations of longer telomeres with worse performance on tests of episodic memory, but only in APOE ε4 carriers (Wikgren et al, 2012a; Wikgren et al, 2012b). Another study found longer telomeres in AD brain tissue than in control brains (Thomas et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

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Short and long telomeres increase risk of amnestic mild cognitive impairment

Roberts

Boardman

Ruth

et al. 2014

Mechanisms of Ageing and Development

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Peripheral blood telomere length has been associated with age-related conditions including Alzheimer’s disease (AD). This suggests that telomere length may identify subjects at increased risk of AD. Thus, we investigated the associations of peripheral blood telomere length with amnestic mild cognitive impairment (aMCI), a putative precursor of AD, among Mayo Clinic Study of Aging participants who were prospectively followed for incident aMCI. We matched 137 incident aMCI cases (mean age 81.1 years, [range 70.9–90.8]; 49.6% men) by age and sex to 137 cognitively normal controls. We measured telomere length (T/S ratio) at baseline and follow-up using quantitative PCR. Compared to the middle T/S quintile (Q3), the risk of aMCI was elevated for subjects with the shortest (Q1: HR, 2.85, 95% Confidence interval [CI] 0.98, 8.25; p = 0.05) and the longest telomere lengths (Q5: HR, 5.58, 95%CI, 2.21, 14.11; p = 0.0003). In this elderly cohort, short and long telomeres were associated with increased risk of aMCI. Our findings suggest that both long and short telomere lengths may play a role in the pathogenesis of aMCI, and may be markers of increased risk of aMCI.

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“…These authors suggested four alternative explanations; 1) an association with endophenotype (hippocampal volume and/or impaired episodic memory), 2) the effects of psychotropic medications, 3) advanced paternal age, and 4) an association with increased mortality. Wikgren et al 38). reported that healthy apolipoprotein E (APOE) ɛ3/ɛ3 individuals with increased TL exhibit reduced hippocampal volumes and that APOE ɛ4 carriers with longer telomeres show poorer performance during episodic memory tasks 39).…”

Section: Discussionmentioning

confidence: 99%

Longer Telomere Length of T lymphocytes in Patients with Early and Chronic Psychosis

Cui

Prabhu

Nguyen

et al. 2017

Clin Psychopharmacol Neurosci

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ObjectiveTo investigate pathological conditions that act as sources of pro-inflammatory cytokines and cytotoxic substances to examine telomere length (TL) in patients with either early (duration of illness [DI] ≤5 years) or chronic (DI >5 years) psychosis using T lymphocytes.MethodsBased on these factors and the important role that T lymphocytes play in inflammation, the present study measured the TL of T lymphocytes in patients with either early or chronic psychosis. Additionally, smoking, metabolic syndrome, depression, and cognitive functioning were assessed to control for confounding effects.ResultsTL was significantly longer in patients with early and chronic psychosis than in healthy control subjects and, moreover, the significance of these findings remained after controlling for age, smoking, metabolic syndrome, DI, chlorpromazine-equivalent dose, and cognitive functioning (F=9.57, degree of freedom=2, p<0.001). Additionally, the DI, chlorpromazine-equivalent doses, and the five-factor scores of the Positive and Negative Syndrome Scale were not significantly correlated with the TL of T lymphocytes in either all patients or each psychosis group.ConclusionPossible mechanisms underlying the effects of antipsychotic medications on telomerase are discussed in the present study, but further studies measuring both telomerase activity and TL using a prospective design will be required.

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APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory

Cited by 44 publications

References 43 publications

Effect of Leukocyte Telomere Length on Total and Regional Brain Volumes in a Large Population-Based Cohort

Effect of Leukocyte Telomere Length on Total and Regional Brain Volumes in a Large Population-Based Cohort

Short and long telomeres increase risk of amnestic mild cognitive impairment

Longer Telomere Length of T lymphocytes in Patients with Early and Chronic Psychosis

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