Presymptomatic apolipoprotein E genotyping for Alzheimer's disease risk assessment and prevention
Corresponding Author
Hyman M. Schipper
Centre for Neurotranslational Research and Bloomfield Centre for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
Corresponding author. Tel.: 514-340-8260; Fax: 514-340-7502.
E-mail address: [email protected]
Search for more papers by this authorCorresponding Author
Hyman M. Schipper
Centre for Neurotranslational Research and Bloomfield Centre for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
Corresponding author. Tel.: 514-340-8260; Fax: 514-340-7502.
E-mail address: [email protected]
Search for more papers by this authorAbstract
Current practice guidelines advocate apolipoprotein E (APOE) genotyping in cases of dementia and mild cognitive impairment and also in asymptomatic participants within the context of clinical/epidemiological research. APOE genotyping is not recommended for prognostication in cognitively intact persons outside the research arena. On the basis of emerging developments, in this article, we revisit the notion that presymptomatic APOE testing might be medically appropriate and ethical for the purpose of Alzheimer's disease (AD) risk assessment and prevention. In support of this thesis, recent evidence is adduced indicating that (i) the potency of potentially modifiable AD determinants and responsiveness to intervention may be affected by the presence or absence of the ɛ4 allele, (ii) disclosure of APOE status to asymptomatic individuals seeking AD risk assessment is well tolerated when appropriate safeguards are in place, and (iii) awareness of personal AD risk in general, and APOE status in particular, may motivate individuals to engage in beneficial, risk-lowering behaviors.
References
- [1]HC Hendrie. Epidemiology of dementia and Alzheimer's disease. Am J Geriatr Psychiatry. 6(2 Suppl 1): 1998; S3–18
- [2]LE Hebert, PA Scherr, JL Bienias, DA Bennett, DA Evans. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 60: 2003; 1119–1122
- [3]H Chertkow, H Bergman, HM Schipper, S Gauthier, R Bouchard, S Fontaine, et al. Assessment of suspected dementia. Can J Neurol Sci. 28(Suppl 1): 2001; S28–S41
- [4]RC Petersen, GE Smith, SC Waring, RJ Ivnik, EG Tangalos, E Kokmen. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 56: 1999; 303–308
- [5]RL Ernst, JW Hay. The US economic and social costs of Alzheimer's disease revisited. Am J Public Health. 84: 1994; 1261–1264
- [6]ZS Khachaturian. A roadmap for the prevention of dementia II: Leon Thal Symposium 2008. Alzheimers Dement. 5: 2009; 85–92
- [7]ZS Khachaturian, AS Khachaturian. Prevent Alzheimer's disease by 2020: a national strategic goal. Alzheimers Dement. 5: 2009; 81–84
- [8]HM Schipper. Apolipoprotein E: implications for AD neurobiology, epidemiology and risk assessment. Neurobiol Aging (in press).
- [9]A Cedazo-Minguez, RF Cowburn, E Apolipoprotein. a major piece in the Alzheimer's disease puzzle. J Cell Mol Med. 5: 2001; 254–266
- [10]VI Zannis, D Kardassis, EE Zanni. Genetic mutations affecting human lipoproteins, their receptors, and their enzymes. Adv Hum Genet. 21: 1993; 145–319
- [11]G-YR Hsiung, AD Sadovnick. Genetics and dementia: risk factors, diagnosis, and management. Alzheimers Dement. 3: 2007; 418–427
- [12]EH Corder, AM Saunders, WJ Strittmatter, DE Schmechel, PC Gaskell, GW Small, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 261: 1993; 921–923
- [13]S Seshadri, DA Drachman, CF Lippa. Apolipoprotein E epsilon 4 allele and the lifetime risk of Alzheimer's disease. What physicians know, and what they should know. Arch Neurol. 52: 1995; 1074–1079
- [14]NT Aggarwal, RS Wilson, TL Beck, JL Bienias, E Berry-Kravis, DA Bennett. The apolipoprotein E epsilon4 allele and incident Alzheimer's disease in persons with mild cognitive impairment. Neurocase. 11: 2005; 3–7
- [15]DP Devanand, GH Pelton, D Zamora, X Liu, MH Tabert, M Goodkind, et al. Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment. Arch Neurol. 62: 2005; 975–980
- [16]GY Hsiung, AD Sadovnick, H Feldman. Apolipoprotein E epsilon4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging. CMAJ. 171: 2004; 863–867
- [17]MC Tierney, JP Szalai, WG Snow, RH Fisher. The prediction of Alzheimer disease. The role of patient and informant perceptions of cognitive deficits. Arch Neurol. 53: 1996; 423–427
- [18] Statement on use of apolipoprotein E testing for Alzheimer disease. American College of Medical Genetics/American Society of Human Genetics Working Group on ApoE and Alzheimer disease. JAMA. 274: 1995; 1627–1629
- [19]H Chertkow. Introduction: the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, 2006. Alzheimers Dement. 3: 2007; 262–265
- [20]RC Petersen, GE Smith, RJ Ivnik, EG Tangalos, DJ Schaid, SN Thibodeau, et al. Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals. JAMA. 273: 1995; 1274–1278
- [21]A Bizzarro, C Marra, A Acciarri, A Valenza, FD Tiziano, C Brahe, et al. Apolipoprotein E epsilon4 allele differentiates the clinical response to donepezil in Alzheimer's disease. Dement Geriatr Cogn Disord. 20: 2005; 254–261
- [22]J Poirier, MC Delisle, R Quirion, I Aubert, M Farlow, D Lahiri, et al. Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proc Natl Acad Sci U S A. 92: 1995; 12260–12264
- [23]JE Hixson, DT Vernier. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 31: 1990; 545–548
- [24]C Patterson, JW Feightner, A Garcia, C MacKnight. General risk factors for dementia: a systematic evidence review. Alzheimers Dement. 3: 2007; 341–347
- [25]R Brookmeyer, S Gray, C Kawas. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 88: 1998; 1337–1342
- [26]C Patterson, JW Feightner, A Garcia, C MacKnight. Primary prevention of dementia. Alzheimers Dement. 3: 2007; 348–354
10.1016/j.jalz.2007.07.005 Google Scholar
- [27]SG Post, PJ Whitehouse, RH Binstock, TD Bird, SK Eckert, LA Farrer, et al. The clinical introduction of genetic testing for Alzheimer disease. An ethical perspective. JAMA. 277: 1997; 832–836
- [28]EW Almqvist, M Bloch, R Brinkman, D Craufurd, MR Hayden. A worldwide assessment of the frequency of suicide, suicide attempts, or psychiatric hospitalization after predictive testing for Huntington disease. Am J Hum Genet. 64: 1999; 1293–1304
- [29]AM Codori, PR Slavney, A Rosenblatt, J Brandt. Prevalence of major depression one year after predictive testing for Huntington's disease. Genet Test. 8: 2004; 114–119
- [30]TB Robins Wahlin. To know or not to know: a review of behaviour and suicidal ideation in preclinical Huntington's disease. Patient Educ Couns. 65: 2007; 279–287
- [31]JS Roberts, LA Cupples, NR Relkin, PJ Whitehouse, RC Green. Genetic risk assessment for adult children of people with Alzheimer's disease: the Risk Evaluation and Education for Alzheimer's Disease (REVEAL) study. J Geriatr Psychiatry Neurol. 18: 2005; 250–255
- [32]RC Green, JS Roberts, LA Cupples, NR Relkin, PJ Whitehouse, T Brown, et al. Disclosure of APOE genotype for risk of Alzheimer's disease. N Engl J Med. 361: 2009; 245–254
- [33]JS Roberts. Anticipating response to predictive genetic testing for Alzheimer's disease: a survey of first-degree relatives. Gerontologist. 40: 2000; 43–52
- [34]JS Roberts, SA LaRusse, H Katzen, PJ Whitehouse, M Barber, SG Post, et al. Reasons for seeking genetic susceptibility testing among first-degree relatives of people with Alzheimer disease. Alzheimer Dis Assoc Disord. 17: 2003; 86–93
- [35]TR Fanshawe, AT Prevost, JS Roberts, RC Green, D Armstrong, TM Marteau. Explaining behavior change after genetic testing: the problem of collinearity between test results and risk estimates. Genet Test. 12: 2008; 381–386
10.1089/gte.2007.0103 Google Scholar
- [36]PH Robert, S Schuck, B Dubois, JP Olie, JP Lepine, T Gallarda, et al. Screening for Alzheimer's disease with the short cognitive evaluation battery. Dement Geriatr Cogn Disord. 15: 2003; 92–98
- [37]CD Zick, CJ Mathews, JS Roberts, R Cook-Deegan, RJ Pokorski, RC Green. Genetic testing for Alzheimer's disease and its impact on insurance purchasing behavior. Health Aff (Millwood). 24: 2005; 483–490
- [38]MR Cassidy, JS Roberts, TD Bird, EJ Steinbart, LA Cupples, CA Chen, et al. Comparing test-specific distress of susceptibility versus deterministic genetic testing for Alzheimer's disease. Alzheimers Dement. 4: 2008; 406–413
- [39]M Lock, J Freeman, G Chilibeck, B Beveridge, M Padolsky. Susceptibility genes and the question of embodied identity. Med Anthropol Q. 21: 2007; 256–276
- [40]SG Post. Future scenarios for the prevention and delay of Alzheimer disease onset in high-risk groups. An ethical perspective. Am J Prev Med. 16: 1999; 105–110
- [41]CM Bojanowski, D Shen, EY Chew, B Ning, KG Csaky, WR Green, et al. An apolipoprotein E variant may protect against age-related macular degeneration through cytokine regulation. Environ Mol Mutagen. 47: 2006; 594–602
- [42]AD Roses, MWLutzHAmrine-MadsenAMSaundersDGCrenshawSS Sundsethet al. A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease. Pharmacogenomics J (in press).
- [43]D Harold, R Abraham, P Hollingworth, R Sims, A Gerrish, ML Hamshere, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet. 41: 2009; 1088–1093