The apolipoprotein e antagonistic pleiotropy hypothesis: review and recommendations

Elizabeth R Tuminello, S Duke Han, Elizabeth R Tuminello, S Duke Han

Abstract

Research on apolipoprotein E (APOE) has consistently revealed a relationship between the gene's ε4 allele and risk for development of Alzheimer's disease (AD). However, research with younger populations of ε4 carriers has suggested that the APOE ε4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an evolutionary biology concept that proposes certain genes or alleles that may differentially impact fitness during different life stages. We critically review this hypothesis in light of new research of the impact of APOE on cognition and neural integrity across the lifespan. We provide recommendations for the revision of the antagonistic pleiotropy hypothesis of APOE and suggest important avenues for future research in this area.

References

    1. Han SD, Bondi MW. Revision of the apolipoprotein E compensatory mechanism recruitment hypothesis. Alzheimer’s and Dementia. 2008;4(4):251–254.
    1. Beffert U, Danik M, Krzywkowski P, Ramassamy C, Berrada F, Poirier J. The neurobiology of apolipoproteins and their receptors in the CNS and Alzheimer’s disease. Brain Research Reviews. 1998;27(2):119–142.
    1. Blom ES, Giedraitis V, Zetterberg H, et al. Rapid progression from mild cognitive impairment to alzheimer’s disease in subjects with elevated levels of tau in cerebrospinal fluid and the Apoe ε4/ε4 genotype. Dementia and Geriatric Cognitive Disorders. 2009;27(5):458–464.
    1. Kukolja J, Thiel CM, Eggermann T, Zerres K, Fink GR. Medial temporal lobe dysfunction during encoding and retrieval of episodic memory in non-demented APOE ε4 carriers. Neuroscience. 2010;168(2):487–497.
    1. Yu YWY, Lin CH, Chen SP, Hong CJ, Tsai SJ. Intelligence and event-related potentials for young female human volunteer apolipoprotein E ε4 and non-ε4 carriers. Neuroscience Letters. 2000;294(3):179–181.
    1. Alexander DM, Williams LM, Gatt JM, et al. The contribution of apolipoprotein E alleles on cognitive performance and dynamic neural activity over six decades. Biological Psychology. 2007;75(3):229–238.
    1. Wright RO, Hu H, Silverman EK, et al. Apolipoprotein E genotype predicts 24-month bayley scales infant development score. Pediatric Research. 2003;54(6):819–825.
    1. Bloss CS, Delis DC, Salmon DP, Bondi MW. APOE genotype is associated with left-handedness and visuospatial skills in children. Neurobiology of Aging. 2010;31(5):787–795.
    1. Marchant NL, King SL, Tabet N, Rusted JM. Positive effects of cholinergic stimulation favor young APOE η4 carriers. Neuropsychopharmacology. 2010;35(5):1090–1096.
    1. Noé E, Ferri J, Colomer C, Moliner B, Chirivella J. APOE genotype and verbal memory recovery during and after emergence from post-traumatic amnesia. Brain Injury. 2010;24(6):886–892.
    1. Dennis NA, Browndyke JN, Stokes J, et al. Temporal lobe functional activity and connectivity in young adult APOE ε4 carriers. Alzheimer's and Dementia. 2010;6(4):303–311.
    1. Filbey FM, Chen G, Sunderland T, Cohen RM. Failing compensatory mechanisms during working memory in older apolipoprotein E-ε4 healthy adults. Brain Imaging and Behavior. 2010;4(2):177–188.
    1. Hiekkanen H, Kurki T, Brandstack N, Kairisto V, Tenovuo O. Association of injury severity, MRI-results and ApoE genotype with 1-year outcome in mainly mild TBI: a preliminary study. Brain Injury. 2009;23(5):396–402.
    1. Luciano M, Gow AJ, Harris SE, et al. Cognitive ability at age 11 and 70 years, information processing speed, and APOE variation: the Lothian Birth Cohort 1936 study. Psychology and Aging. 2009;24(1):129–138.
    1. Ruiz JR, Castillo R, Labayen I, et al. Individual and combined effects of ApoE and MTHFR 677C/T polymorphisms on cognitive performance in Spanish adolescents: the AVENA study. Journal of Pediatrics. 2010;156(6):978–984.
    1. Bloss CS, Delis DC, Salmon DP, Bondi MW. Decreased cognition in children with risk factors for Alzheimer's disease. Biological Psychiatry. 2008;64(10):904–906.
    1. Acevedo SF, Piper BJ, Craytor MJ, Benice TS, Raber J. Apolipoprotein E4 and sex affect neurobehavioral performance in primary school children. Pediatric Research. 2010;67(3):293–299.
    1. Filippini N, MacIntosh BJ, Hough MG, et al. Distinct patterns of brain activity in young carriers of the APOE-ε4 allele. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(17):7209–7214.
    1. Trivedi MA, Schmitz TW, Ries ML, et al. fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: Risk factors for Alzheimer’s disease. Neuropsychologia. 2008;46(6):1667–1678.
    1. Wierenga CE, Stricker NH, McCauley A, et al. Increased functional brain response during word retrieval in cognitively intact older adults at genetic risk for Alzheimer’s disease. NeuroImage. 2010;51(3):1222–1233.
    1. Seidenberg M, Guidotti L, Nielson KA, et al. Semantic memory activation in individuals at risk for developing Alzheimer disease. Neurology. 2009;73(8):612–620.
    1. Woodard JL, Seidenberg M, Nielson KA, et al. Semantic memory activation in amnestic mild cognitive impairment. Brain. 2009;132(8):2068–2078.
    1. Bartrés-Faz D, Serra-Grabulosa JM, Sun FT, et al. Functional connectivity of the hippocampus in elderly with mild memory dysfunction carrying the APOE ε4 allele. Neurobiology of Aging. 2008;29(11):1644–1653.
    1. Borghesani PR, Johnson LC, Shelton AL, et al. Altered medial temporal lobe responses during visuospatial encoding in healthy APOE∗4 carriers. Neurobiology of Aging. 2008;29(7):981–991.
    1. Xu G, Mclaren DG, Ries ML, et al. The influence of parental history of Alzheimer’s disease and apolipoprotein E ε4 on the BOLD signal during recognition memory. Brain. 2009;132(2):383–391.
    1. Suthana NA, Krupa A, Donix M, et al. Reduced hippocampal CA2, CA3, and dentate gyrus activity in asymptomatic people at genetic risk for Alzheimer’s disease. NeuroImage. 2010;53(3):1077–1084.
    1. Welsh-Bohmer KA, Ostbye T, Sanders L, et al. Neuropsychological performance in advanced age: influences of demographic factors and apolipoprotein E: findings from the Cache County memory study. Clinical Neuropsychologist. 2009;23(1):77–99.
    1. Adamson MM, Landy KM, Duong S, et al. Apolipoprotein E epsilon4 influences on episodic recall and brain structures in aging pilots. Neurobiology of Aging. 2010;31(6):1059–1063.
    1. Debette S, Wolf PA, Beiser A, et al. Association of parental dementia with cognitive and brain MRI measures in middle-aged adults. Neurology. 2009;73(24):2071–2078.
    1. Honea RA, Vidoni E, Harsha A, Burns JM. Impact of APOE on the healthy aging brain: a voxel-based MRI and DTI study. Journal of Alzheimer’s Disease. 2009;18(3):553–564.
    1. Caselli RJ, Dueck AC, Osborne D, et al. Longitudinal growth modeling of cognitive aging and the APOE e4 effect. The New England Journal of Medicine. 2009;361(3):255–263.
    1. De Blasi S, Montesanto A, Martino C, et al. APOE polymorphism affects episodic memory among non demented elderly subjects. Experimental Gerontology. 2009;44(3):224–227.
    1. Knopman DS, Mosley TH, Catellier DJ, Coker LH. Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study. Alzheimer’s and Dementia. 2009;5(3):207–214.
    1. Mungas D, Beckett L, Harvey D, et al. Heterogeneity of cognitive trajectories in diverse older persons. Psychology and Aging. 2010;25(3):606–619.
    1. Walhovd KB, Fjell AM, Dale AM, et al. Multi-modal imaging predicts memory performance in normal aging and cognitive decline. Neurobiology of Aging. 2010;31(7):1107–1121.
    1. Hayden KM, Zandi PP, West NA, et al. Effects of family history and apolipoprotein E ε4 status on cognitive decline in the absence of Alzheimer dementia: the cache county study. Archives of Neurology. 2009;66(11):1378–1383.
    1. Whitehair DC, Sherzai A, Emond J, et al. Influence of apolipoprotein E varepsilon4 on rates of cognitive and functional decline in mild cognitive impairment. Alzheimer's & Dementia. 2010;6(5):412–419.
    1. Yaffe K, Fiocco AJ, Lindquist K, et al. Predictors of maintaining cognitive function in older adults: the health ABC study. Neurology. 2009;72(23):2029–2035.
    1. Thambisetty M, Beason-Held L, An Y, Kraut MA, Resnick SM. APOE ε4 genotype and longitudinal changes in cerebral blood flow in normal aging. Archives of Neurology. 2010;67(1):93–98.
    1. Raz N, Rodrigue KM, Kennedy KM, Land S. Genetic and vascular modifiers of age-sensitive cognitive skills: effects of COMT, BDNF, ApoE, and hypertension. Neuropsychology. 2009;23(1):105–116.
    1. Barabash A, Marcos A, Ancín I, et al. APOE, ACT and CHRNA7 genes in the conversion from amnestic mild cognitive impairment to Alzheimer’s disease. Neurobiology of Aging. 2009;30(8):1254–1264.
    1. Wang PN, Liu HC, Lirng JF, Lin KN, Wu ZA. Accelerated hippocampal atrophy rates in stable and progressive amnestic mild cognitive impairment. Psychiatry Research. 2009;171(3):221–231.
    1. Heun R, Gühne U, Luck T, et al. Apolipoprotein E allele 4 is not a sufficient or a necessary predictor of the development of Mild Cognitive Impairment. European Psychiatry. 2010;25(1):15–18.
    1. Carrión-Baralt JR, Meléndez-Cabrero J, Rodríguez-Ubias H, et al. Impact of APOE ε4 on the cognitive performance of a sample of non-demented puerto rican nonagenarians. Journal of Alzheimer’s Disease. 2009;18(3):533–540.
    1. Kozauer NA, Mielke MM, Chuen Chan GK, Rebok GW, Lyketsos CG. Apolipoprotein E genotype and lifetime cognitive decline. International Psychogeriatrics. 2008;20(1):109–123.
    1. Mondadori CRA, De Quervain DJF, Buchmann A, et al. Better memory and neural efficiency in young apolipoprotein E ε4 carriers. Cerebral Cortex. 2007;17(8):1934–1947.
    1. Gozal D, Capdevila OS, Kheirandish-Gozal L, Crabtree VM. APOE ε4 allele, cognitive dysfunction, and obstructive sleep apnea in children. Neurology. 2007;69(3):243–249.
    1. Liu F, Pardo LM, Schuur M, et al. The apolipoprotein E gene and its age-specific effects on cognitive function. Neurobiology of Aging. 2008;31(10):1831–1833.
    1. Filbey FM, Slack KJ, Sunderland TP, Cohen RM. Functional magnetic resonance imaging and magnetoencephalography differences associated with APOEε4 in young healthy adults. NeuroReport. 2006;17(15):1585–1590.
    1. Trachtenberg AJ, Filippini N, Mackay CE. The effects of APOE-ε4 on the BOLD response. Neurobiology of Aging. In press.
    1. Bookheimer SY, Strojwas MH, Cohen MS, et al. Patterns of brain activation in people at risk for Alzheimer’s disease. New England Journal of Medicine. 2000;343(7):450–456.
    1. Dickerson BC, Salat DH, Greve DN, et al. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology. 2005;65(3):404–411.
    1. Bondi MW, Houston WS, Eyler LT, Brown GG. fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease. Neurology. 2005;64(3):501–508.
    1. Johnson SC, Ries ML, Hess TM, et al. Effect of alzheimer disease risk on brain function during self-appraisal in healthy middle-aged adults. Archives of General Psychiatry. 2007;64(10):1163–1171.
    1. Johnson SC, Schmitz TW, Trivedi MA, et al. The influence of Alzheimer disease family history and apolipoprotein E ε4 on mesial temporal lobe activation. Journal of Neuroscience. 2006;26(22):6069–6076.
    1. Lind J, Persson J, Ingvar M, et al. Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers. Brain. 2006;129(5):1240–1248.
    1. D’Esposito M, Deouell LY, Gazzaley A. Alterations in the bold fMRI signal with ageing and disease: a challenge for neuroimaging. Nature Reviews Neuroscience. 2003;4(11):863–872.
    1. Bangen KJ, Restom K, Liu TT, et al. Differential age effects on cerebral blood flow and BOLD response to encoding: associations with cognition and stroke risk. Neurobiology of Aging. 2009;30(8):1276–1287.
    1. Chuang YF, Hayden KM, Norton MC, et al. Association between APOE ε4 allele and vascular dementia: the cache county study. Dementia and Geriatric Cognitive Disorders. 2010;29(3):248–253.
    1. Zade D, Beiser A, McGlinchey R, et al. Interactive effects of apolipoprotein E type 4 genotype and cerebrovascular risk on neuropsychological performance and structural brain changes. Journal of Stroke and Cerebrovascular Diseases. 2010;19(4):261–268.
    1. Fiocco AJ, Nair NPV, Schwartz G, et al. Influence of genetic polymorphisms in the apolipoprotein (APOE) and the butyrylcholinesterase (BCHE) gene on stress markers in older adults: a 3-year study. Neurobiology of Aging. 2009;30(6):1001–1005.
    1. Reinvang I, Lundervold AJ, Wehling E, Rootwelt H, Espeseth T. Epistasis between APOE and nicotinic receptor gene CHRNA4 in age related cognitive function and decline. Journal of the International Neuropsychological Society. 2010;16(3):424–432.
    1. Qiu C, Fratiglioni L. Apolipoprotein E epsilon4 status and cognitive decline with and without dementia. Archives of Neurology. 2010;67(8):p. 1036.
    1. Van Der Walt A, Stankovich J, Bahlo M, et al. Apolipoprotein genotype does not influence MS severity, cognition, or brain atrophy. Neurology. 2009;73(13):1018–1025.
    1. Brys M, Pirraglia E, Rich K, et al. Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment. Neurobiology of Aging. 2009;30(5):682–690.
    1. Reiman EM, Chen K, Liu X, et al. Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(16):6820–6825.
    1. Reitz C, Mayeux R. Endophenotypes in normal brain morphology and Alzheimer’s disease: a review. Neuroscience. 2009;164(1):174–190.
    1. Shaw LM, Vanderstichele H, Knapik-Czajka M, et al. Cerebrospinal fluid biomarker signature in alzheimer’s disease neuroimaging initiative subjects. Annals of Neurology. 2009;65(4):403–413.
    1. Vemuri P, Wiste HJ, Weigand SD, et al. Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease. Annals of Neurology. 2010;67(3):308–316.
    1. Fjell AM, Walhovd KB, Fennema-Notestine C, et al. CSF biomarkers in prediction of cerebral and clinical change in mild cognitive impairment and Alzheimer’s disease. Journal of Neuroscience. 2010;30(6):2088–2101.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi