The Apolipoprotein E Gene, Attention, and Brain Function

Overview

Journal Neuropsychology

Publisher American Psychological Association

Specialty Neurology

Date 2002 Apr 13

PMID 11949718

Citations 44

Authors

Raja Parasuraman

Pamela M Greenwood

Trey Sunderland

Affiliations

Soon will be listed here.

Abstract

The epsilon4 allele of the apolipoprotein E (ApoE) gene is associated with alterations in brain function and is a risk factor for Alzheimer's disease (AD). Changes in components of visuospatial attention with ApoE-epsilon4, aging, and AD are described. Healthy middle-aged adults without dementia who have the ApoE-epsilon4 gene show deficits in spatial attention and working memory that are qualitatively similar to those seen in clinically diagnosed AD patients. The findings support an association between ApoE polymorphism and specific components of visuospatial attention. Molecular mechanisms that may mediate the ApoE-attention link by modulating cholinergic neurotransmission to the posterior parietal cortex are discussed. Studies of attention and brain function in ApoE-epsilon4 carriers without dementia can advance knowledge of the genetics of visual attention, may enhance understanding of the preclinical phase of AD, and may lead to better methods for early AD detection.

Citing Articles

Stimulation of Locus Ceruleus Inputs to the Prelimbic Cortex in Mice Induces Cell Type-Specific Expression of the Gene.

Craig G, Ramos L, Essig S, Eagles N, Jaffe A, Martinowich K eNeuro. 2024; 11(12).

PMID: 39632090 PMC: 11675532. DOI: 10.1523/ENEURO.0328-24.2024.

Overexpression of the gene in the frontal cortex of mice causes sex-dependent changes in learning, attention, and anxiety-like behavior.

Ramos L, Harr A, Zakas F, Essig S, Kempskie G, Fadil N bioRxiv. 2024; .

PMID: 39149404 PMC: 11326296. DOI: 10.1101/2024.08.08.607225.

Stimulation of locus coeruleus inputs to the frontal cortex in mice induces cell type-specific expression of the gene.

Craig G, Ramos L, Essig S, Eagles N, Jaffe A, Martinowich K bioRxiv. 2024; .

PMID: 39091890 PMC: 11291023. DOI: 10.1101/2024.07.22.604695.

Genetic polymorphisms and post-stroke upper limb motor improvement - A systematic review and meta-analysis.

Subramanian S, Morgan R, Rasmusson C, Shepherd K, Li C J Cent Nerv Syst Dis. 2024; 16:11795735241266601.

PMID: 39049838 PMC: 11268047. DOI: 10.1177/11795735241266601.

Effects of Exercise Training and L-Arginine Loaded Chitosan Nanoparticles on Hippocampus Histopathology, β-Secretase Enzyme Function, APP, Tau, Iba1and APOE-4 mRNA in Aging Rats.

Feizolahi F, Arabzadeh E, Sarshin A, Falahi F, Dehghannayeri Z, Ali Askari A Neurotox Res. 2024; 42(2):21.

PMID: 38441819 DOI: 10.1007/s12640-024-00699-y.

References

Feskens E, Havekes L, Kalmijn S, de Knijff P, Launer L, Kromhout D . Apolipoprotein e4 allele and cognitive decline in elderly men. BMJ. 1994; 309(6963):1202-6. PMC: 2541698. DOI: 10.1136/bmj.309.6963.1202. View

Posner M, Dehaene S . Attentional networks. Trends Neurosci. 1994; 17(2):75-9. DOI: 10.1016/0166-2236(94)90078-7. View

Koch C, Ullman S . Shifts in selective visual attention: towards the underlying neural circuitry. Hum Neurobiol. 1985; 4(4):219-27. View

Katzman R . Education and the prevalence of dementia and Alzheimer's disease. Neurology. 1993; 43(1):13-20. DOI: 10.1212/wnl.43.1_part_1.13. View

McGaughy J, Everitt B, Robbins T, Sarter M . The role of cortical cholinergic afferent projections in cognition: impact of new selective immunotoxins. Behav Brain Res. 2000; 115(2):251-63. DOI: 10.1016/s0166-4328(00)00262-x. View

Farrer L, Cupples L, Haines J, Hyman B, Kukull W, Mayeux R . Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997; 278(16):1349-56. View

Buck B, Black S, Behrmann M, Caldwell C, Bronskill M . Spatial- and object-based attentional deficits in Alzheimer's disease. Relationship to HMPAO-SPECT measures of parietal perfusion. Brain. 1997; 120 ( Pt 7):1229-44. DOI: 10.1093/brain/120.7.1229. View

Robinson D, Bowman E, Kertzman C . Covert orienting of attention in macaques. II. Contributions of parietal cortex. J Neurophysiol. 1995; 74(2):698-712. DOI: 10.1152/jn.1995.74.2.698. View

Nestor P, Parasuraman R, Haxby J, Grady C . Divided attention and metabolic brain dysfunction in mild dementia of the Alzheimer's type. Neuropsychologia. 1991; 29(5):379-87. DOI: 10.1016/0028-3932(91)90026-5. View

10.

Gecz J, Mulley J . Genes for cognitive function: developments on the X. Genome Res. 2000; 10(2):157-63. DOI: 10.1101/gr.10.2.157. View

11.

Moceri V, Kukull W, EMANUEL I, van Belle G, Larson E . Early-life risk factors and the development of Alzheimer's disease. Neurology. 2000; 54(2):415-20. DOI: 10.1212/wnl.54.2.415. View

12.

Fink G, Halligan P, Marshall J, Frith C, Frackowiak R, Dolan R . Where in the brain does visual attention select the forest and the trees?. Nature. 1996; 382(6592):626-8. DOI: 10.1038/382626a0. View

13.

Corbetta M, Shulman G, Miezin F, Petersen S . Superior parietal cortex activation during spatial attention shifts and visual feature conjunction. Science. 1995; 270(5237):802-5. DOI: 10.1126/science.270.5237.802. View

14.

Greenwood P, Sunderland T, Friz J, Parasuraman R . Genetics and visual attention: selective deficits in healthy adult carriers of the epsilon 4 allele of the apolipoprotein E gene. Proc Natl Acad Sci U S A. 2000; 97(21):11661-6. PMC: 17257. DOI: 10.1073/pnas.97.21.11661. View

15.

Whalley L, Starr J, Athawes R, Hunter D, Pattie A, Deary I . Childhood mental ability and dementia. Neurology. 2000; 55(10):1455-9. DOI: 10.1212/wnl.55.10.1455. View

16.

Arriagada P, Marzloff K, Hyman B . Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease. Neurology. 1992; 42(9):1681-8. DOI: 10.1212/wnl.42.9.1681. View

17.

Duncan J . Selective attention and the organization of visual information. J Exp Psychol Gen. 1984; 113(4):501-17. DOI: 10.1037//0096-3445.113.4.501. View

18.

Iyo M, Namba H, Fukushi K, Shinotoh H, Nagatsuka S, Suhara T . Measurement of acetylcholinesterase by positron emission tomography in the brains of healthy controls and patients with Alzheimer's disease. Lancet. 1997; 349(9068):1805-9. DOI: 10.1016/S0140-6736(96)09124-6. View

19.

Flory J, Manuck S, Ferrell R, Ryan C, Muldoon M . Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults. Am J Med Genet. 2000; 96(6):707-11. DOI: 10.1002/1096-8628(20001204)96:6<707::aid-ajmg1>3.0.co;2-v. View

20.

Corbetta M, Kincade J, Ollinger J, McAvoy M, Shulman G . Voluntary orienting is dissociated from target detection in human posterior parietal cortex. Nat Neurosci. 2000; 3(3):292-7. DOI: 10.1038/73009. View