Apolipoprotein E genotype and outcome in infants with hypoxic–ischemic encephalopathy

In this chapter we summarize the NICHD Neonatal Research Network (NRN) trial of whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy in relation to other randomized controlled trials (RCTs) of hypothermia neuroprotection. We describe the NRN secondary studies that have been published in the last 10 years evaluating clinical, genetic, biochemical and imaging biomarkers of outcome.

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“…CP prevalence was also similar between groups. Thus, disability was not associated with APOE genotype among survivors of neonatal HIE 40 .…”

Section: Biomarkers Of Outcomementioning

confidence: 81%

Hypothermia for neonatal hypoxic–ischemic encephalopathy: NICHD Neonatal Research Network contribution to the field

Shankaran

Natarajan

Chalak

et al. 2016

Seminars in Perinatology

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“…A dermatology clinic in Spain reported that APOE 4 carriers were significantly more frequent in patients with severe psoriasis compared to controls (p = 0.003) and to non-severe psoriasis (p = 0.017). Infants with hypoxic-ischemic encephalopathy did not show an association with APOE allele type [72]. In contrast, the percentage of children with at least one 4 allele was significantly lower in non-Sudden infant death syndrome (SIDS) compared to SIDS (p = 0.016) in a study of infants from Scotland.…”

Section: Co-morbidities In Young Apolipoprotein 4 Carriers (Table 3)mentioning

confidence: 84%

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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“…Recently, another group of investigators showed that APOE gene and weight at birth are risk factors for future cardiovascular diseases, and these factors seem to be independent factors as well [114]. To note, nonetheless, that these latter findings make the possible mechanistic (molecular) correlations among APOE , cholesterol metabolism, and vascular diseases much less linear than what could have been expected earlier [115,116]. Furthermore, data in support of the interaction between APOE alleles and environment suggest that a specific APOE genotype is a risk factor able to potentiate the toxic effects of various environmental contaminants.…”

Section: Apoe Polymorphism In Normal and Pathologic Conditions Of Thementioning

confidence: 99%

Impact of Apolipoprotein E gene polymorphism during normal and pathological conditions of the brain across the lifespan

Iacono

Feltis

2019

Aging

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The central nervous system (CNS) is the cellular substrate for the integration of complex, dynamic, constant, and simultaneous interactions among endogenous and exogenous stimuli across the entire human lifespan. Numerous studies on aging-related brain diseases show that some genes identified as risk factors for some of the most common neurodegenerative diseases - such as the allele 4 of APOE gene (APOE4) for Alzheimer’s disease (AD) - have a much earlier neuro-anatomical and neuro-physiological impact. The impact of APOE polymorphism appears in fact to start as early as youth and early-adult life. Intriguingly, though, those same genes associated with aging-related brain diseases seem to influence different aspects of the brain functioning much earlier actually, that is, even from the neonatal periods and earlier. The APOE4, an allele classically associated with later-life neurodegenerative disorders as AD, seems in fact to exert a series of very early effects on phenomena of neuroplasticity and synaptogenesis that begin from the earliest periods of life such as the fetal ones.We reviewed some of the findings supporting the hypothesis that APOE polymorphism is an early modifier of various neurobiological aspects across the entire human lifespan - from the in-utero to the centenarian life - during both normal and pathological conditions of the brain.

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Apolipoprotein E genotype and outcome in infants with hypoxic–ischemic encephalopathy

Cited by 10 publications

References 41 publications

Hypothermia for neonatal hypoxic–ischemic encephalopathy: NICHD Neonatal Research Network contribution to the field

Hypothermia for neonatal hypoxic–ischemic encephalopathy: NICHD Neonatal Research Network contribution to the field

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

Impact of Apolipoprotein E gene polymorphism during normal and pathological conditions of the brain across the lifespan

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