Sex and APOE: A memory advantage in male APOE ε4 carriers in midlife

Zokaei, Nahid; Giehl, Kathrin; Sillence, Annie; Neville, Matt J.; Karpe, Fredrik; Nobre, Anna C.

doi:10.1016/j.cortex.2016.12.016

Cited by 40 publications

(53 citation statements)

References 41 publications

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“…APOE ε4–positive men with SCD and especially APOE ε4–negative men with SCD showed strong associations with incident MCI. This exhibits similarities to Zokaei et al [30] reporting a memory advantage in midlife for male APOE ε4 carriers. This is in contrast to studies in old‐aged participants, where APOE ε4 carriers show worse memory performance compared with noncarriers.…”

Section: Discussionsupporting

confidence: 85%

Subjective cognitive decline, APOE ε4, and incident mild cognitive impairment in men and women

Müller-Gerards

Weimar

Abramowski

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction Possible joint effects of subjective cognitive decline (SCD) and apolipoprotein E ( APOE ) ε4 genotype on incident mild cognitive impairment (MCI) were examined for men and women separately. Methods Cognitively normal participants with and without SCD were included from the first follow-up examination of the population-based Heinz Nixdorf Recall study. Sex-stratified logistic regression models estimated main effects and interactions (additive, multiplicative) of SCD at the first follow-up (yes+/no−) and APOE ε4 (positive+/negative−) groups for MCI 5 years later. Results Odds for MCI 5 years later were higher in SCD/ APOE ε4 group +/+ than the sum of groups +/− and −/+ in women, with a trend for positive interaction. Odds for incident MCI in men was highest in group +/−, with no interaction effect. Discussion Our findings indicate that APOE ε4 may play an important role in the association of SCD and incident MCI, especially considering sex. Further studies need to examine these associations with larger sample sizes.

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Section: Discussionsupporting

confidence: 85%

Subjective cognitive decline, APOE ε4, and incident mild cognitive impairment in men and women

Müller-Gerards

Weimar

Abramowski

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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show abstract

“…In particular, the observed variation in AAO mirrors the variation in human patients reported by Ryman and colleagues (Ryman et al, 2014), suggesting our panel captures a portion of the phenotypic heterogeneity observed in human FAD patients. In addition, our female AD-BXD mice appear to be more susceptible to Apoe risk and AD-related cognitive decline ( Figures 2B and 2C) despite comparable levels of amy-loid deposition ( Figures 1F and 1G), 5XFAD transgene expression ( Figure 1H), and endogenous App levels ( Figure 1I), similar to epidemiological trends observed in human patients (Altmann et al, 2014;Mielke et al, 2014;Zokaei et al, 2017). At the genetic level, we demonstrate that the extent of AD-related cognitive decline is influenced by a given strain's specific allele distribution across a set of 21 loci associated with sporadic LOAD.…”

Section: Ad-bxd Panel Represents a New Translational Model Of Human Adsupporting

confidence: 81%

Harnessing Genetic Complexity to Enhance Translatability of Alzheimer’s Disease Mouse Models: A Path toward Precision Medicine

Neuner

Heuer

Huentelman

et al. 2019

Neuron

179

271

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“…Several studies have reported better performance on memory tasks in young subjects possessing the 4 allele [131][132][133][134][135][136]. Comparatively enhanced verbal fluency has also been observed in 4 allele carriers [137,104].…”

Section: Mental Performance In Young Apolipoprotein 4 Carriers (Table 8)mentioning

confidence: 99%

Putative Survival Advantages in Young Apolipoprotein ɛ4 Carriers are Associated with Increased Neural Stress

Smith

Ashford

Perfetti³

2019

JAD

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Inheritance of a single copy of the apolipoprotein E (APOE) 4 allele increases risk of Alzheimer's disease (AD) by 3-4-fold, with homozygosity associated with a 12-16-fold increase in risk, relative to 3 allele homozygosity. There is a decreased risk associated with the APOE 2 allele. The pathological consequence of APOE genotype has led to intense efforts to understand the mechanistic basis of the interplay between APOE status and loss of synapses. Numerous 4 allele-related associations have been reported with the potential relevance of these associations to the pathogenesis of AD unknown at this time. In primarily young subjects, we have reviewed a representative body of literature on 4 allele-associations related to the following: cardiovascular responses; impacts on reproduction and fetal development; co-morbidities; resistance to infectious disease; responses to head injury; biochemical differences possibly related to neural stress; and brain structure-function differences. In addition, the literature on the association between the 4 allele and cognitive performance has been reviewed comprehensively. The weight-of-the-evidence supports the hypothesis that possession of the ancestral 4 allele in youth is associated with improved fitness during fetal development, infancy, and youth relative to the more recently appearing 3 allele, at the expense of decreased fitness in old age, which is substantially improved by the 3 allele. However, possession of the 4 allele is also associated with higher levels of synaptic macromolecular turnover, which likely stresses basic cellular neuroplasticity mechanisms. Clinical trials of potential AD therapeutics should consider APOE status as an enrollment criterion. conceptualization of AD pathology dates from 1968 when Blessed et al. showed in elderly individuals that the NFTs correlated with the severity of the dementia, though the neuritic plaques, which contain cerebral amyloid-␤ (A␤), did not [2]. A major advance in understanding AD pathology was the demonstration that AD pathology predominantly affects the posterior-temporal, inferior parietal, posterior cingulate, and medial temporal region [3], with a characteristic pattern of progression beginning in the entorhinal cortex involving neurofibrillary (NF)

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Sex and APOE: A memory advantage in male APOE ε4 carriers in midlife

Cited by 40 publications

References 41 publications

Subjective cognitive decline, APOE ε4, and incident mild cognitive impairment in men and women

Subjective cognitive decline, APOE ε4, and incident mild cognitive impairment in men and women

Harnessing Genetic Complexity to Enhance Translatability of Alzheimer’s Disease Mouse Models: A Path toward Precision Medicine

Putative Survival Advantages in Young Apolipoprotein ɛ4 Carriers are Associated with Increased Neural Stress

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