Preliminary Report of a Genetic Basis for Cognitive Decline After Cardiac Operations 11The members of the Neurologic Outcome Research Group of the Duke Heart Center are listed in Appendix A.

Tardiff, Barbara E.; Newman, Mark F.; Saunders, Ann M.; Strittmatter, Warren J.; Blumenthal, James A.; White, William D.; Croughwell, Narda D.; Davis, R. Benjamin; Roses, Allen D.; Rêves, J. G.

doi:10.1016/s0003-4975(97)00757-1

Cited by 241 publications

(77 citation statements)

References 19 publications

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“…6 ApoE4 has also been implicated in poor neurological recovery after head injury, cerebral hemorrhage, and cardiac bypass surgery. [7][8][9][10][11][12] In addition, ApoE4 was suggested to act as a risk factor for bulbar-onset amyotrophic lateral sclerosis, for Pick's disease, corticobasal degeneration, and progressive supranuclear palsy (characterized by protein Tau-related cytoskeletal pathology), and for inclusion body myositis, although contradictory results have been found. [13][14][15][16][17][18][19] Epidemiological data do not provide evidence for a direct role of ApoE in central nervous system disorders, and its mechanism of action within the central nervous system is not clear.…”

mentioning

confidence: 99%

Prominent Axonopathy and Disruption of Axonal Transport in Transgenic Mice Expressing Human Apolipoprotein E4 in Neurons of Brain and Spinal Cord

Tesseur

Dorpe

Bruynseels

et al. 2000

The American Journal of Pathology

131

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The epsilon 4 allele of the human apolipoprotein E gene (ApoE4) constitutes an important genetic risk factor for Alzheimer's disease. Recent experimental evidence suggests that human ApoE is expressed in neurons, in addition to being synthesized in glial cells. Moreover, brain regions in which neurons express ApoE seem to be most vulnerable to neurofibrillary pathology. The hypothesis that the expression pattern of human ApoE might be important for the pathogenesis of Alzheimer's disease was tested by generating transgenic mice that express human ApoE4 in neurons or in astrocytes of the central nervous system. Transgenic mice expressing human ApoE4 in neurons developed axonal degeneration and gliosis in brain and in spinal cord, resulting in reduced sensorimotor capacities. In these mice, axonal dilatations with accumulation of synaptophysin, neurofilaments, mitochondria, and vesicles were documented, suggesting impairment of axonal transport. In contrast, transgenic mice expressing human ApoE4 in astrocytes remained normal throughout life. These results suggest that expression of human ApoE in neurons of the central nervous system could contribute to impaired axonal transport and axonal degeneration. The epsilon 4 allele of the apolipoprotein E (ApoE) gene is associated with Alzheimer's disease (AD), affecting the onset of the disease in an allele dose-dependent manner. 1,2 ApoE4 is associated with increased plaque load in AD 3-5 and early onset of neurofibrillary changes. 6 ApoE4 has also been implicated in poor neurological recovery after head injury, cerebral hemorrhage, and cardiac bypass surgery. [7][8][9][10][11][12] In addition, ApoE4 was suggested to act as a risk factor for bulbar-onset amyotrophic lateral sclerosis, for Pick's disease, corticobasal degeneration, and progressive supranuclear palsy (characterized by protein Tau-related cytoskeletal pathology), and for inclusion body myositis, although contradictory results have been found. [13][14][15][16][17][18][19] Epidemiological data do not provide evidence for a direct role of ApoE in central nervous system disorders, and its mechanism of action within the central nervous system is not clear. Originally, it was thought that ApoE present in neurons originated only from endocytosis. 20 -22 Numerous cell culture experiments demonstrated receptor-mediated uptake of ApoE as well as effects on neurite outgrowth and cell-morphology. [23][24][25][26][27][28][29] However, more and more evidence indicates that intraneuronal ApoE might also originate from synthesis by neurons. In situ hybridization of brain sections of transgenic mice expressing genomic fragments containing the entire human ApoE locus, including its promoter sequences, revealed expression in neurons, besides astrocytes. 30 -32 Human neuroblastoma cells were shown to synthesize both ApoE mRNA and protein. 33,34 Moreover, in situ hybridization of human brain sections conclusively demonstrated ApoE mRNA in neurons. 35 Taken together these results suggest that besides its well-known synthesis...

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mentioning

confidence: 99%

Prominent Axonopathy and Disruption of Axonal Transport in Transgenic Mice Expressing Human Apolipoprotein E4 in Neurons of Brain and Spinal Cord

Tesseur

Dorpe

Bruynseels

et al. 2000

The American Journal of Pathology

131

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“…A dominant APOE4 genetic model was used in this study based on the available literature. [7][8][9][10][11] It is possible that other APOE alleles might correlate with cognitive outcome in a more robust fashion, although post hoc analyses did not suggest that this is the case. A more expansive evaluation of genetic factors, as we had conducted in the cardiac surgical population, may have yielded a significant association.…”

Section: Discussionmentioning

confidence: 99%

“…However, clinical evidence over the past decade has been conflicting. 11,12,13 APOE4 has also been implicated in the proinflammatory response. 14,15,16,17 This link between APOE4 and a heightened inflammatory response along with reports of association between plasma inflammatory markers and POCD, 18 suggest that APOE4, inflammation, and POCD may be interlinked.…”

Section: Introductionmentioning

confidence: 99%

Cognitive Function After Major Noncardiac Surgery, Apolipoprotein E4 Genotype, and Biomarkers of Brain Injury

&NA;

2010

Survey of Anesthesiology

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“…Genetic variants have been found for adverse events such as myocardial ischemia [53], postoperative arrhythmias [54], vein graft restenosis [55], transplant rejection [56], renal compromise [57,58], neurocognitive dysfunction [59,60], stroke [61], and death [62], as well as more systemic outcomes such as bleeding [63], thrombosis [64], inflammatory responses and severe sepsis [65], and alterations in vascular reactivity [66] (see Podgoreanu [2]). Even more broadly, genetic variants affecting inflammatory responses have been identified.…”

Section: Genomic Variability and Complex Diseasementioning

confidence: 99%

Pharmacogenomics and end-organ susceptibility to injury in the perioperative period

Schwinn

Podgoreanu

2008

Best Practice & Research Clinical Anaesthesiology

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Genomic medicine has provided new mechanistic understanding for many complex diseases over the last 5-10 years. More recently genomic approaches have been applied to the perioperative paradigm, facilitating identification of patients at high risk for adverse events, as well as those who will respond better/worse to specific pharmacologic therapies. The consistent biological theme emerging is that while inflammation is important in healing from surgical trauma, patients who are too robustly proinflammatory appear to be at higher risk for adverse perioperative events. Precise predictors of each adverse event are being elucidated so that corrective therapeutics can be instituted to improve outcomes in high-risk patients. While the field of perioperative genomics could be considered in its infancy, such approaches are the wave of the future.

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Preliminary Report of a Genetic Basis for Cognitive Decline After Cardiac Operations 11The members of the Neurologic Outcome Research Group of the Duke Heart Center are listed in Appendix A.

Cited by 241 publications

References 19 publications

Prominent Axonopathy and Disruption of Axonal Transport in Transgenic Mice Expressing Human Apolipoprotein E4 in Neurons of Brain and Spinal Cord

Prominent Axonopathy and Disruption of Axonal Transport in Transgenic Mice Expressing Human Apolipoprotein E4 in Neurons of Brain and Spinal Cord

Cognitive Function After Major Noncardiac Surgery, Apolipoprotein E4 Genotype, and Biomarkers of Brain Injury

Pharmacogenomics and end-organ susceptibility to injury in the perioperative period

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