Behavior Genetics

, Volume 36, Issue 2, pp 185–194

Longitudinal Memory Performance During Normal Aging: Twin Association Models of APOE and Other Alzheimer Candidate Genes

  • Chandra A. Reynolds
  • Jonathan A. Prince
  • Lars Feuk
  • Anthony J. Brookes
  • Margaret Gatz
  • Nancy L. Pedersen
Article

Abstract

The APOE gene (apolipoprotein E) is a major risk factor for Alzheimer’s Disease (AD) but has been inconsistently associated with memory in nondemented adults. Two other genes with mixed support as genetic risk factors for AD, A2M (alpha-2-macroglobulin) and LRP (low-density lipoprotein receptor-related protein), have not been studied in relation to memory among nondemented adults. The present study examined these three genes and latent growth parameters estimated from memory performance spanning 13 years in 478 twins from the Swedish Adoption/Twin Study of Aging (SATSA). APOE was associated with working and recall memory ability levels and working memory rate of change, with e4 homozygotes exhibiting the worst performance at all ages. Homozygotes for the rare A2M insertion/deletion variant exhibited accelerating decline on delayed figural recognition. There were no significant findings for LRP. Dominance, often untested in previous studies, was important in the current study’s findings.

Keywords

A2M APOE association memory twins 

References

  1. Bennett D. A., Wilson R. S., Schneider J. A., Evans D. A., Mendes de Leon C. F., Arnold S. E., Barnes L. L. and Bienias J. L. (2003). Education modifies the relation of AD pathology to level of cognitive function in older persons. Neurology 60: 1909–1915PubMedGoogle Scholar
  2. Blacker D., Wilcox M. A., Laird N. M., Rodes L., Horvath S. M., Go R.C., Perry R., Watson B. Jr., Bassett S. S., McInnis M. G., Albert M. S., Hyman B. T. and Tanzi R. E. (1998). Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat. Genet. 19: 357–360PubMedCrossRefGoogle Scholar
  3. Bondi M. W., Salmon D. P., Galasko D., Thomas R. G. and Thal L. J. (1999). Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer’s disease. Psychol. Aging 14: 295–303PubMedCrossRefGoogle Scholar
  4. Bretsky P., Guralnik J. M., Launer L., Albert M. and Seeman T. E. (2003). The role of APOE-epsilon4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging. Neurology 60: 1077–1081PubMedGoogle Scholar
  5. Caselli R. J., Osborne D., Reiman E. M., Hentz J. G., Barbieri C. J., Saunders A. M., Hardy J., Graff-Radford N. R., Hall G. R. and Alexander G. E. (2001). Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study. J. Neurol. Sci. 189: 93–98PubMedCrossRefGoogle Scholar
  6. Caselli R. J., Reiman E. M., Osborne D., Hentz J. G., Baxter L. C., Hernandez J. L. and Alexander G. G. (2004). Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele. Neurology 62: 1990–1995PubMedGoogle Scholar
  7. DeFries J. C., Plomin R., Vandenberg S. G. and Kuse A. R. (1981). Parent–offspring resemblance for cognitive abilities in the Colorado Adoption Project: Biological, adoptive, and control parents and one-year-old children. Intelligence 5: 245–277CrossRefGoogle Scholar
  8. Farrer L. A., Cupples L. A., Haines J. L., Hyman B., Kukull W. A., Mayeux R., Myers R. H., Pericak-Vance M. A., Risch N., and van Duijn C. M. (1997). 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 278: 1349–1356PubMedCrossRefGoogle Scholar
  9. Finch C. E. and Tanzi R. E. (1997). Genetics of aging. Science 278: 407–411PubMedCrossRefGoogle Scholar
  10. Finkel D. and McGue M. (1993). The origins of individual differences in memory among the elderly: A behavior genetic analysis. Psychol. Aging 8: 527–537PubMedCrossRefGoogle Scholar
  11. Finkel D. and McGue M. (1998). Age differences in the nature and origin of individual differences in memory: a behavior genetic analysis [In Process Citation]. Int. J. Aging Hum. Dev. 47: 217–239PubMedGoogle Scholar
  12. Flory J. D., Manuck S. B., Ferrell R. E., Ryan C. M. and Muldoon M. F. (2000). Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults. Am. J. Med. Genet. 96: 707–711PubMedCrossRefGoogle Scholar
  13. Fulker D. W., Cherny S. S., Sham P. C. and Hewitt J. K. (1999). Combined linkage and association sib-pair analysis for quantitative traits. Am. J. Hum. Genet. 64: 259–267PubMedCrossRefGoogle Scholar
  14. Gatz M., Pedersen N. L., Berg S., Johansson B., Johansson K., Mortimer J. A., Posner S. F., Viitanen M., Winblad B. and Ahlbom A. (1997). Heritability for Alzheimer’s disease: The study of dementia in Swedish twins. J. Gerontol. Med. Sci. 52: M117–125Google Scholar
  15. Green M. S., Kaye J. A. and Ball M. J. (2000). The Oregon brain aging study: Neuropathology accompanying healthy aging in the oldest old. Neurology 54: 105–113PubMedCrossRefGoogle Scholar
  16. Johansson B., Hofer S. M., Allaire J. C., Maldonado-Molina M. M., Piccinin A. M., Berg S., Pedersen N. L. and McClearn G. E. (2004). Change in cognitive capabilities in the oldest old: the effects of proximity to death in genetically related individuals over a 6-year period. Psychol. Aging 19: 145–156PubMedCrossRefGoogle Scholar
  17. Johansson B., Whitfield K., Pedersen N. L., Hofer S. M., Ahern F. and McClearn G. E. (1999). Origins of individual differences in episodic memory in the oldest-old: a population-based study of identical and same-sex fraternal twins aged 80 and older. J. Gerontol. B Psychol. Sci. Soc. Sci. 54: P173–179PubMedGoogle Scholar
  18. Jonsson C. -O. and Molander L. (1964). Manual till CVB-skalan [Manual of the CVB Scales]. Psykologi Förlaget, StockholmGoogle Scholar
  19. Lahiri D. K., Sambamurti K. and Bennett D. A. (2004). Apolipoprotein gene and its interaction with the environmentally driven risk factors: molecular, genetic and epidemiological studies of Alzheimer’s disease. Neurobiol. Aging 25: 651–660PubMedCrossRefGoogle Scholar
  20. Lambert J. C., Wavrant-De Vrieze F., Amouyel P. and Chartier-Harlin M. C. (1998). Association at LRP gene locus with sporadic late-onset alzheimer’s disease. Lancet 351: 1787–1788PubMedCrossRefGoogle Scholar
  21. Lee J. H., Flaquer A., Stern Y., Tycko B. and Mayeux R. (2004). Genetic influences on memory performance in familial Alzheimer disease. Neurology 62: 414–421PubMedGoogle Scholar
  22. Lopes M. B., Bogaev C. A., Gonias S. L. and VandenBerg S. R. (1994). Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein is increased in reactive and neoplastic glial cells. FEBS Lett. 338: 301–305PubMedCrossRefGoogle Scholar
  23. Mayeux R., Small S. A., Tang M., Tycko B. and Stern Y. (2001). Memory performance in healthy elderly without Alzheimer’s disease: Effects of time and apolipoprotein-E. Neurobiol. Aging 22: 683–689PubMedCrossRefGoogle Scholar
  24. McClearn G. E., Johansson B., Berg S., Pedersen N. L., Ahern F., Petrill S. A. and Plomin R. (1997). Substantial genetic influence on cognitive abilities in twins 80 or more years old. Science 276: 1560–1563PubMedCrossRefGoogle Scholar
  25. Neale M. C., Boker S. M., Xie G. and Maes H. H. (1999). Mx: Statistical Modeling. Department of Psychiatry, VCU Box 900126, Richmond, VAGoogle Scholar
  26. Neale M. C., Cherny S. S., Sham P. C., Whitfield J. B., Heath A. C., Birley A. J. and Martin N. G. (1999). Distinguishing population stratification from genuine allelic effects with Mx: Association of ADH2 with alcohol consumption. Behav. Genet. 29: 233–243CrossRefGoogle Scholar
  27. Pedersen N. L., McClearn G. E., Plomin R., Nesselroade J. R., Berg S. and DeFaire U. (1991). The Swedish Adoption/Twin Study of Aging: An update. Acta Geneticae Medicae et Gemellologiae: Twin Res. 40: 7–20Google Scholar
  28. Pedersen N. L., Plomin R., Nesselroade J. R. and McClearn G. E. (1992). A quantitative genetic analysis of cognitive abilities during the second half of the life span. Psychol. Sci. 3: 346–353CrossRefGoogle Scholar
  29. Pedersen N. L., Ripatti S., Berg S., Reynolds C., Hofer S. M., Finkel D., Gatz M. and Palmgren J. (2003). The influence of mortality on twin models of change: addressing missingness through multiple imputation. Behav. Genet. 33: 161–169PubMedCrossRefGoogle Scholar
  30. Plomin R. and Spinath F. M. (2004). Intelligence: Genetics, genes, and genomics. J. Pers. Soc. Psychol. 86: 112–129PubMedCrossRefGoogle Scholar
  31. Posthuma D., de Geus E. J., Boomsma D. I. and Neale M. C. (2004). Combined linkage and association tests in mx. Behav. Genet. 34: 179–196PubMedCrossRefGoogle Scholar
  32. Posthuma D., Neale M. C., Boomsma D. I. and de Geus E. J. C. (2001). Are smarter brains running faster? Heritability of alpha peak frequency, IQ, and their interrelation. Behav. Genet. 31: 567–579PubMedCrossRefGoogle Scholar
  33. Puglielli L., Tanzi R. E. and Kovacs D. M. (2003). Alzheimer’s disease: The cholesterol connection. Nat. Neurosci. 6: 345–351PubMedCrossRefGoogle Scholar
  34. Rebeck G. W., Harr S. D., Strickland D. K. and Hyman B. T. (1995). Multiple, diverse senile plaque-associated proteins are ligands of an apolipoprotein E receptor, the alpha 2-macroglobulin receptor/low-density-lipoprotein receptor-related protein. Ann. Neurol. 37: 211–217PubMedCrossRefGoogle Scholar
  35. Reiman E. M., Chen K., Alexander G. E., Caselli R. J., Bandy D., Osborne D., Saunders A. M. and Hardy J. (2004). Functional brain abnormalities in young adults at genetic risk for late-onset alzheimer’s dementia. PNAS 101: 284–289PubMedCrossRefGoogle Scholar
  36. Reynolds C. A., Finkel D., McArdle J. J., Gatz M., Berg S., and Pedersen N. L. (2005). Quantitative genetic analysis of latent growth curve models of cognitive abilities in adulthood. Dev. Psychol. 41: 3–16PubMedCrossRefGoogle Scholar
  37. Riley K. P., Snowdon D. A., Saunders A. M., Roses A. D., Mortimer J. A. and Nanayakkara N. (2000). Cognitive function and apolipoprotein E in very old adults: findings from the Nun Study. J. Gerontol. B Psychol. Sci. Soc. Sci. 55: S69–75PubMedGoogle Scholar
  38. Ripatti S., Gatz M., Pedersen N. L. and Palmgren J. (2003). Three-state frailty model for age at onset of dementia and death in Swedish twins. Genet. Epidemiol. 24: 139–149PubMedCrossRefGoogle Scholar
  39. SAS. (1999). SAS online documentation for Windows (Version Release 8). SAS Institute Inc., Cary, NCGoogle Scholar
  40. Sanchez-Guerra M., Combarros O., Infante J., Llorca J., Berciano J., Fontalba A., Fernandez-Luna J. L., Pena N. and Fernandez-Viadero C. (2001). Case-control study and meta-analysis of low density lipoprotein receptor-related protein gene exon 3 polymorphism in Alzheimer’s disease. Neurosci. Lett. 316: 17–20PubMedCrossRefGoogle Scholar
  41. Saunders A. J., Bertram L., Mullin K., Sampson A. J., Latifzai K., Basu S., Jones J., Kinney D., MacKenzie-Ingano L., Yu S., Albert M. S., Moscarillo T. J., Go R. C., Bassett S. S., Daly M. J., Laird N. M., Wang X., Velicelebi G., Wagner S. L., Becker D. K., Tanzi R. E. and Blacker D. (2003). Genetic association of Alzheimer’s disease with multiple polymorphisms in alpha-2-macroglobulin. Hum. Mol. Genet. 12: 2765–2776PubMedCrossRefGoogle Scholar
  42. Schmitt F. A., Davis D. G., Wekstein D. R., Smith C. D., Ashford J. W. and Markesbery W. R. (2000). “Preclinical” AD revisited: neuropathology of cognitively normal older adults. Neurology 55: 370–376PubMedGoogle Scholar
  43. Small B. J., Graves A. B., McEvoy C. L., Crawford F. C., Mullan M. and Mortimer J. A. (2000). Is APOE – epsilon4 a risk factor for cognitive impairment in normal aging? Neurology 54: 2082–2088PubMedGoogle Scholar
  44. Smith G. E., Bohac D. L., Waring S. C., Kokmen E., Tangalos E. G., Ivnik R. J. and Petersen R. C. (1998). Apolipoprotein E genotype influences cognitive ‘phenotype’ in patients with Alzheimer’s disease but not in healthy control subjects. Neurology 50: 355–362PubMedGoogle Scholar
  45. Strittmatter W. J., Saunders A. M., Schmechel D., Pericak-Vance M., Enghild J., Salvesen G. S. and Roses A. D. (1993). Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. USA 90: 1977–1981PubMedCrossRefGoogle Scholar
  46. Swanson H. L. (1999). What develops in working memory? A life span perspective. Dev. Psychol. 35: 986–1000PubMedCrossRefGoogle Scholar
  47. Thurstone L. L. (1948). Primary Mental Abilities. University of Chicago Press, ChicagoGoogle Scholar
  48. Warzok R. W., Kessler C., Apel G., Schwarz A., Egensperger R., Schreiber D., Herbst E. W., Wolf E., Walther R. and Walker L. C. (1998). Apolipoprotein E4 promotes incipient Alzheimer pathology in the elderly. Alzheimer Dis. Assoc. Disord. 12: 33–39PubMedCrossRefGoogle Scholar
  49. Wilson R. S., Schneider J. A., Barnes L. L., Beckett L. A., Aggarwal N. T., Cochran E. J., Berry-Kravis E., Bach J., Fox J. H., Evans D. A. and Bennett D. A. (2002). The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period. Arch. Neurol. 59: 1154–1160PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Chandra A. Reynolds
    • 1
    • 6
  • Jonathan A. Prince
    • 2
  • Lars Feuk
    • 2
  • Anthony J. Brookes
    • 2
    • 3
  • Margaret Gatz
    • 4
    • 5
  • Nancy L. Pedersen
    • 4
    • 5
  1. 1.Department of PsychologyUniversity of California – RiversideRiversideUSA
  2. 2.Center for Genomics and BioinformaticsKarolinska InstitutetStockholmSweden
  3. 3.Department of GeneticsLeicester UniversityLeicesterUK
  4. 4.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
  5. 5.Department of PsychologyUniversity of Southern CaliforniaLos AngelesUSA
  6. 6.Department of PsychologyUniversity of California – RiversideRiversideUSA

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