ApoE-ε4 is associated with reduced memory in long-standing intractable temporal lobe epilepsy

Busch, Robyn M.; Lineweaver, Tara T.; Naugle, Richard I.; Kim, K. H.; Gong, Yunhua; Tilelli, Cristiane Queixa; Prayson, Richard A.; Bingaman, William; Najm, Imad; Diaz‐Arrastia, Ramon

doi:10.1212/01.wnl.0000253021.60887.db

Cited by 46 publications

(37 citation statements)

References 37 publications

(13 reference statements)

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“…Interestingly, the ɛ4 allele was also associated with decreased memory abilities in a subsample of patients from the current study who had longstanding epilepsy, further highlighting the effect of ɛ4 on these individuals (Busch et al, 2007). It is possible that ɛ4 is associated with more global cognitive dysfunction compared to those without ɛ4, resulting in decreased ability to compensate during the postictal period.…”

Section: Discussionmentioning

confidence: 57%

“…Two individuals were excluded due to unavailable postictal confusion data, resulting in a sample of 85 individuals who underwent anterior temporal lobectomy for the treatment of medically intractable TLE (right = 42; left = 43). A detailed description of participant characteristics and inclusion criteria are reported elsewhere (Busch et al, 2007). Briefly, patients were included in the study if they had a Full Scale IQ of 70 or higher and had frozen or paraffin-embedded tissue that underwent DNA analysis.…”

Section: Methodsmentioning

confidence: 99%

“…APOE status was determined by DNA extracted from 20 mg of frozen or paraffin-embedded brain tissue obtained at time of surgery. For additional details regarding the methods used for DNA genotyping, please see Busch et al (2007).…”

Section: Methodsmentioning

confidence: 99%

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APOE ɛ4 is associated with postictal confusion in patients with medically refractory temporal lobe epilepsy

et al. 2008

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SummaryThis study examined the relationship between the APOE ɛ4 allele and postictal confusion in patients with medically intractable temporal lobe epilepsy (TLE). Patients with at least one ɛ4 allele (n = 22) were three times more likely to exhibit postictal confusion (68%) than the 63 patients without ɛ4 (43%). These preliminary results demonstrate that APOE ɛ4 is associated with an increased risk of postictal confusion in patients with medically intractable TLE, suggesting possible dysfunction in neuronal recovery mechanisms.

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Section: Discussionmentioning

confidence: 57%

Section: Methodsmentioning

confidence: 99%

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APOE ɛ4 is associated with postictal confusion in patients with medically refractory temporal lobe epilepsy

et al. 2008

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“…For the APOE gene, many studies have found that its polymorphism is strongly correlated with different kinds of epilepsy. The ApoE-ε allele interacts with longstanding seizures to affect verbal and nonverbal memory performance in patients with medically intractable temporal lobe epilepsy [13]. This allele also increases the risk of postictal confusion [14].…”

Section: Resultsmentioning

confidence: 99%

Exploring Candidate Genes for Epilepsy by Computational Disease-Gene Identification Strategy

Sha

Liu

Wang

et al. 2010

Balkan Journal of Medical Genetics

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Epilepsy is a complex disease with a strong genetic component. So far, studies have focused on experimental validation or genome-wide linkage scans for epilepsy susceptibility genes in multiple populations. We have used four bioinformatic tools (SNPs3D, PROSPECTR and SUSPECTS, GenWanderer, PosMed) to analyze 16 susceptibility loci selected from a literature search. Pathways and regulatory network analyses were performed using the Ingenuity Pathways Analysis (IPA) software. We identified a subset of 48 candidate epilepsy susceptibility genes. Five significant canonical pathways, in four typical networks, were identified: GABA receptor signaling, interleukin-6 (IL-6) signaling, G-protein coupled receptor signaling, type 2 diabetes mellitus signaling and airway inflammation in asthma. We concluded that online analytical tools provide a powerful way to reveal candidate genes which can greatly reduce experimental time. Our study contributes to further experimental tests for epilepsy susceptibility genes.

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“…In humans, E4 carriers exhibit reduced cognitive capacity, reductions in resting brain glucose metabolism, and a distinct pattern of brain activity that is observed well before onset of AD symptoms [35][36][37]. Furthermore, the apoE4 allele is positively linked to subclinical epileptiform activity, which is remarkable in light of the recent compelling evidence showing that aberrant excitatory neuronal activity is a primary upstream mechanism for cognitive decline in AD [38][39][40][41]. In mice that express human apoE4, dendritic architecture, spine number, and electrophysiological parameters are significantly reduced when compared to age-and background-matched mice expressing human apoE3 [42].…”

Section: Synapse Loss As Both Cause and Effect In Admentioning

confidence: 96%

Phosphodiesterase Inhibition to Target the Synaptic Dysfunction in Alzheimer’s Disease

Bales

Plath

Svenstrup

et al. 2010

Topics in Medicinal Chemistry

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Alzheimer's Disease (AD) is a disease of synaptic dysfunction that ultimately proceeds to neuronal death. There is a wealth of evidence that indicates the final common mediator of this neurotoxic process is the formation and actions on synaptotoxic b-amyloid (Ab). The premise in this review is that synaptic dysfunction may also be an initiating factor in for AD and promote synaptotoxic Ab formation. This latter hypothesis is consistent with the fact that the most common risk factors for AD, apolipoprotein E (ApoE) allele status, age, education, and fitness, encompass suboptimal synaptic function. Thus, the synaptic dysfunction in AD may be both cause and effect, and remediating synaptic dysfunction in AD may have acute effects on the symptoms present at the initiation of therapy and also slow disease progression. The cyclic nucleotide (cAMP and cGMP) signaling systems are intimately involved in the regulation of synaptic homeostasis. The phosphodiesterases (PDEs) are a superfamily of enzymes that critically regulate spatial and temporal aspects of cyclic nucleotide signaling through metabolic inactivation of cAMP and cGMP. Thus, targeting the PDEs to promote improved synaptic function, or 'synaptic resilience', may be an effective and facile approach to new symptomatic and disease modifying therapies for AD. There continues to be a significant drug discovery effort aimed at discovering PDE inhibitors to treat a variety of neuropsychiatric disorders. Here we review the current status of those efforts as they relate to potential new therapies for AD.

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ApoE-ε4 is associated with reduced memory in long-standing intractable temporal lobe epilepsy

Abstract: The ApoE-epsilon4 allele interacts with longstanding seizures to affect memory performance, both verbal and nonverbal, in patients with medically intractable temporal lobe epilepsy.

Cited by 46 publications

References 37 publications

APOE ɛ4 is associated with postictal confusion in patients with medically refractory temporal lobe epilepsy

APOE ɛ4 is associated with postictal confusion in patients with medically refractory temporal lobe epilepsy

Exploring Candidate Genes for Epilepsy by Computational Disease-Gene Identification Strategy

Phosphodiesterase Inhibition to Target the Synaptic Dysfunction in Alzheimer’s Disease

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