The clinical introduction of genetic testing for Alzheimer disease. An ethical perspective
JAMAPublished 12 March 1997
S. G. Post
Citations177
SJR quartileQ1
SJR score5.35
SNIP10.71
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Abstract
Except for autosomal dominant early-onset families, genetic testing in asymptomatic individuals is unwarranted. Use of APOE genetic testing as a diagnostic adjunct in patients already presenting with dementia may prove useful but it remains under investigation. The premature introduction of genetic testing and possible adverse consequences are to be avoided.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
ScienceGene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
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NatureFamilial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene
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New England Journal of MedicinePreclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E
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ScienceCharacterization and Chromosomal Localization of a cDNA Encoding Brain Amyloid of Alzheimer's Disease
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NatureEarly-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene
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Choice Reviews OnlineDeciding for others: the ethics of surrogate decision making
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ScienceGenetic Linkage Evidence for a Familial Alzheimer's Disease Locus on Chromosome 14
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Annual Review of MedicineAPOLIPOPROTEIN E ALLELES AS RISK FACTORS IN ALZHEIMER'S DISEASE
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Proceedings of the National Academy of SciencesApolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease.
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JAMAApolipoprotein E Type 4 Allele and Cerebral Glucose Metabolism in Relatives at Risk for Familial Alzheimer Disease
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The inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD, and glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.
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Annals of NeurologyThe apolipoprotein ε4 allele in patients with Alzheimer's disease
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The data confirm the association between AD and APO‐ε4 and support the hypothesis that the APO'ε4 allele either confers genetic susceptibility to AD or may be in linkage disequilibrium with another susceptibility locus and Ethnic variability in the allelic frequency of APO•ε4 in the elderly warrants further investigation.
Milbank QuarterlyEstimated Prevalence of Alzheimer's Disease in the United States
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NeurologyApolipoprotein E element 4 association with dementia in a population-based study
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Evidence for an association of apoE epsilon4 with other dementia, primarily multi-infarct dementia and stroke and the low positive predictive value of this marker suggest that use of ApoE genotyping as a screening test for AD is not supported.
Journal of Neuropathology & Experimental NeurologyApolipoprotein E Affects the Rate of Alzheimer Disease Expression: β-Amyloid Burden Is a Secondary Consequence Dependent on APOE Genotype and Duration of Disease
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ScienceGenetic Discrimination: Perspectives of Consumers
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Human Molecular GeneticsAlzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant
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Analysis of additional members of a pedigree known to segregate a Met239Val mutation in PS-2 revealed that the age of onset of symptoms is highly variable (range 45-88 years), and this variability is not attributable to differences in ApoE genotypes.
NeurologyRisk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study
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The data suggest that women are innately more susceptible to AD than men, the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease, and AD may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research.
The LancetSpecificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease
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In this necropsy-confirmed series, the epsilon 4/epsilon 4 genotype predicted AD with 100% accuracy and was unexpectedly highly specific for AD.
NeuroreportA mutation in Alzheimerʼs disease destroying a splice acceptor site in the presenilin-1 gene
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JAMAStatement on Use of Apolipoprotein E Testing for Alzheimer Disease
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There is general consensus that APOE epsilon 4 is strongly associated with AD and that when present may represent an important risk factor for the disease, however, at the present time it is not recommended for use in routine clinical diagnosis nor should it be used for predictive testing.
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The use of APOE genotyping to predict future risk of AD in symptom-free individuals is not recommended and it should not be used as the sole diagnostic test for AD.
New England Journal of MedicineEvaluation of Dementia
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Annals of NeurologyApolipoprotein E genotype in patients with alzheimer's disease: Implications for the risk of dementia among relatives
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Annals of NeurologyApolipoprotein E genotypes and age of onset in early‐onset familial Alzheimer's disease
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PubMedEthical and legal dilemmas arising during predictive testing for adult-onset disease: the experience of Huntington disease.
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American Journal of Public HealthApolipoprotein E and Alzheimer's disease: the implications of progress in molecular medicine.
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Clinics in Geriatric MedicineDifferential Diagnosis of Alzheimer’s Disease
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Characterization of phenotypic variants of AD and refinement of diagnostic criteria for the non-AD dementias is needed to clarify the inter-relationships of these conditions and facilitate molecular genetic and other basic investigations of the etiopathogenesis of AD.
Annals of NeurologyWhy do DNA testing? Practical and ethical implications of new neurogenetic tests
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PubMedGenetic counseling in a Swedish Alzheimer family with amyloid precursor protein mutation.
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Genetic counseling in three family members is described, believed to be the first time presymptomatic genetic testing for AD has been reported, in members of the family who were at risk of inheriting the disease and who demanded the information.
PubMedHuntington disease and the abuse of genetics.
32 Citations1992Peter S. Harper
This disorder provides a valuable example of how abuses in the past need to be recognized and confronted, if the authors are to avoid their recurrence in relation to new molecular and computing techniques in genetics.
Alzheimer Disease & Associated DisordersIssues in Molecular Genetic Testing of Individuals with Suspected Early-onset Familial Alzheimerʼs Disease
15 Citations1994Harry Karlinsky, A. Dessa Sadovnick +4 more
Although molecular genetic testing in particular individuals, such as the man described herein, could be appropriate, it should not be interpreted in general at this stage to individuals suspected of having AD.