APOE in the normal brain

Flowers, Sarah A.; Rebeck, G. William

doi:10.1016/j.nbd.2019.104724

Cited by 92 publications

(86 citation statements)

References 169 publications

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“…We focused on the comparison between individuals at standard genetic risk for AD (ε3ε3; hereafter non-carriers) and individuals at increased genetic risk for AD in heterozygosis (ε3ε4; hereafter; carriers) since sample sizes were insufficient to separately study the effects ε2 carriage (linked to reduced risk of AD but increased risk of type III hyperlipoproteinemia [24]) and ε4 carriage in homozygosis. Nevertheless, excluded genotypes are known to alter molecular and cellular dynamics [24,25], which could potentially interfere with the neurophysiological response to exercise, and therefore, we decided not to group together all ε4-carrying (ε2ε4, ε3ε4, ε4ε4) and all ε4-non-carrying (ε2ε2, ε2ε3, ε3ε3) genotypes. Among the remaining 127 participants, there were 36 APOE ε4 carriers and 91 non-carriers.…”

Section: Methodsmentioning

confidence: 99%

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The relationship between physical activity, apolipoprotein E ε4 carriage, and brain health

et al. 2020

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Background: Neuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer's disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms of APOE ε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one sample may strengthen our understanding of this complex phenomenon. Method: The relationship between PA and functional connectivity (FC) was examined in a sample of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. The correlation between FC and brain structural integrity, cognition, and mood was also investigated. Results: A relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all individuals (across the whole sample, in ε4 carriers, and in ε4 non-carriers), but its effects manifest differently according to genetic risk. In ε4 carriers, we report an association between this region-specific FC profile and preserved brain structure (greater gray matter volumes and higher integrity of white matter tracts). In this group, decreased FC also correlated with reduced anxiety levels. In ε4 non-carriers, this profile is associated with improved cognition (working and episodic memory). Conclusions: PA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all individuals, especially ε4 carriers.

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Section: Methodsmentioning

confidence: 99%

“…Artifact-free data were segmented in 4 s epochs. Then, MEG time series were filtered into delta (2-4 Hz), theta (4-8 Hz), alpha (8)(9)(10)(11)(12), and beta (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). This procedure has been reported in detail in [22].…”

Section: Data Acquisition and Signal Preprocessingmentioning

confidence: 99%

The relationship between physical activity, apolipoprotein E ε4 carriage, and brain health

et al. 2020

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“…Several studies have demonstrated that the APOE ε4 allele is an independent risk factor for Alzheimer's dementia (Strittmatter et al, 1993). Besides, the associations with the APOE have been observed in several other central nervous system diseases, such as dementia with Lewy bodies, recovery of stroke, and risk of cognitive impairment after chemotherapy (Flowers and Rebeck, 2020). However, the relationship between the APOE ε4 allele and vascular dementia is still controversial (Zekry et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E ε4 Is Associated With the Development of Incident Dementia in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Patients With p.Arg544Cys Mutation

Lee

Ko²,

et al. 2020

Front. Aging Neurosci.

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Background and PurposeTo identify clinical, laboratory, and magnetic resonance imaging (MRI) features in predicting incident stroke and dementia in Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).Materials and MethodsWe enrolled 87 Korean CADASIL patients who had undergone baseline clinical, laboratory, and MRI examinations between March 2012 and February 2015. The primary outcome of this study is the occurrence of stroke and dementia during the study period. The occurrence of incident stroke was confirmed by neuroimaging study, and dementia was defined by the diagnostic and statistical manual of mental disorders, fourth edition, criteria.ResultsOf the 87 patients, 57.5% were men, and the mean age was 63 ± 13 years (range 34–90 years), and 82 patients (94.3%) had p.Arg544Cys mutation. During an average follow-up of 67 months (interquartile range: 53–69 months), incident stroke occurred in 14 of 87 patients (16.1%) and incident dementia in 7 of 70 non-demented patients (10.0%). In adjusted analysis, increased systolic blood pressure was associated with increased risk of incident stroke [for every 10-mmHg increase; hazard ratio, 1.44 (1.02–2.03)]. Apolipoprotein E ε4 genotype was associated with an increased risk of incident dementia [hazard ratio, 10.70 (1.27–89.88)].ConclusionIn this study, apolipoprotein E ε4 genotype was associated with the development of incident dementia, and higher blood pressure was associated with increased risk of incident stroke in CADASIL patients with predominant p.Arg544Cys mutation.

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“…Nevertheless, excluded genotypes are known to alter molecular and cellular dynamics (24,25), which could potentially interfere with the neurophysiological response to exercise and therefore we decided not to group together all ε4 carrying (ε2ε4, ε3ε4, ε4ε4) and all ε4 non-carrying carrying (ε2ε2, ε2ε3, ε3ε3) genotypes. Among the remaining 127 participants, there were 3 6 APOE ε4 carriers and 91 noncarriers.…”

Section: Methodsmentioning

confidence: 99%

“…Artifact-free data were segmented in 4 seconds epochs. Then MEG time series were filtered into delta (2-4Hz), theta (4-8Hz), alpha (8-12Hz) and beta (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). This procedure has been reported in detailed in (22).…”

Section: Magnetoencephalographymentioning

confidence: 99%

The relationship between physical activity, apolipoprotein E ε4 carriage and brain health

Frutos-Lucas

Cuesta

López‐Sanz

et al. 2020

Preprint

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BACKGROUND: Neuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer’s disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms of APOE ε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one sample may strengthen our understanding of this complex phenomenon. METHOD: The relationship between PA and functional connectivity (FC) was examined in a sample of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. The correlation between FC and brain structural integrity, cognition and mood was also investigated. RESULTS: A relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all individuals (across the whole sample, in ε4 carriers and in ε4 non-carriers), but its effects manifest differently according to genetic risk. In ε4 carriers, we report an association between this region-specific FC profile and preserved brain structure (greater gray matter volumes and higher integrity of white matter tracts). In this group decreased FC also correlated with reduced anxiety levels. In ε4 non-carriers, this profile is associated with improved cognition (working and episodic memory). CONCLUSIONS: PA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all individuals, specially ε4 carriers.

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APOE in the normal brain

Cited by 92 publications

References 169 publications

The relationship between physical activity, apolipoprotein E ε4 carriage, and brain health

The relationship between physical activity, apolipoprotein E ε4 carriage, and brain health

Apolipoprotein E ε4 Is Associated With the Development of Incident Dementia in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Patients With p.Arg544Cys Mutation

The relationship between physical activity, apolipoprotein E ε4 carriage and brain health

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