Apolipoprotein-E genotyping in diagnosis of Alzheimer's disease

Kakulas, B. A.; Wilton, Steve D.; Fabian, V.; Jones, TM

doi:10.1016/s0140-6736(05)64588-6

Cited by 39 publications

(14 citation statements)

References 5 publications

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“…Studies, assessing the usefulness of the APOE genotype in the diagnosis of AD among persons with dementia, reported specificities of the e4 allele between 81 and 100% 64–67 when used in combination with clinical or autopsy criteria but lower specificities when used alone 65 . Sensitivity estimates were lower and ranged between 19–75% 64,65,67,68 …”

Section: Genetics Of Load and Its Endophenotypesmentioning

confidence: 99%

Use of Genetic Variation as Biomarkers for Alzheimer's Disease

Reitz

Mayeux

2009

Annals of the New York Academy of Sciences

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Late-onset Alzheimer's disease (LOAD) is the most common cause of late-onset dementia in western societies. Despite remarkable achievements in human genetics throughout the years, in particular technological advances in gene mapping and in statistical methods that relate genetic variants to disease, to date only a small proportion of the genetic contribution to LOAD can be explained leaving several remaining genetic risk factors to be identified. A possible explanation for the difficulty in gene identification is that LOAD is a multifactorial complex disorder with both genetic and environmental components. Multiple genes with small effects each ("quantitative trait loci" [QTLs]) are likely to contribute to the quantitative traits associated with the disease, such as memory performance, amyloid/tau pathology, or hippocampal atrophy. The motivation for identifying the genetics of LOAD is clear. Not only could it shed light on disease pathogenesis, but it may also provide potential targets for effective treatment, screening, and prevention. Here, we review the usefulness of genetic variation as diagnostic tools and biomarkers in LOAD and discuss the potentials and difficulties researchers face in designing appropriate studies for gene discovery.

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Section: Genetics Of Load and Its Endophenotypesmentioning

confidence: 99%

Use of Genetic Variation as Biomarkers for Alzheimer's Disease

Reitz

Mayeux

2009

Annals of the New York Academy of Sciences

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“…The Royal Perth Hospital (RPH) series is of unusual interest and suggests that the entrance criteria affects sensitivity but does not substantially change PPV 17. In other words, the ɛ4 allele would have been useful for diagnosis in a lower percentage of patients when only the words 'dementia' or 'AD' (instead of clinical criteria obtained during life) are used for case selection of autopsies performed over a ten‐year period.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Apolipoprotein E and ALzheimer's Disease: The Tip of the Susceptibility Iceberg

Roses¹

1998

Annals of the New York Academy of Sciences

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Apolipoprotein E (APOE) is a true susceptibility polymorphism of the common form of Alzheimer's disease (AD). There are three APOE alleles (epsilon 2, epsilon 3, epsilon 4) that are universally distributed in the population with some variation in allele frequency due to racial and ethnic differences, and are associated with different risks and age of onset distributions. In multiple studies, the positive predictive value for symptomatic possible or probable AD patients who carry at least one epsilon 4 allele was consistently > 95%. Thus, early in the clinical course of dementia, when diagnoses are only 60-70% accurate, the presence of an epsilon 4 allele raises the diagnostic accuracy of AD to 95%. With the anticipation of a second major late-onset AD susceptibility locus on chromosome 12, a matrix of relative susceptibility risks in the population raises many ethical and social questions associated with preclinical prediction. The metabolism of apoE (protein) in the brain is a new and exciting area of neurobiology research made relevant by the association with AD. We have constructed transgenic animals using large human genomic fragments containing human APOE on an APOE-deficit mouse background as well as homologous recombination experiments replacing mouse APOE with human APOE promoter elements. The APOE tissue elements, NOT the human APOE gene coding sequence, is associated with the human pattern of intraneuronal apoE immunoreactivity.

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“…Several studies assessed the specificity and sensitivity of ApoE genotyping in the diagnosis of AD. The sensitivity of ApoE genotyping for the diagnosis of AD varied and it ranged from 19% to 75% 67-70). Mayeux et al68) assessed the specificity and sensitivity of ApoE genotyping, clinical diagnosis and the combination of both techniques in more than 2000 AD patients.…”

Section: Genetic Variations As Markers For Alzheimer's Diseasementioning

confidence: 99%

Panel of Genetic Variations as a Potential Non-invasive Biomarker for Early Diagnosis of Alzheimer's Disease

Lam

2011

Clin Psychopharmacol Neurosci

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Alzheimer's disease (AD) is the most prevalent form of dementia. Biomarkers such as levels of amyloid beta (Aβ) in cerebrospinal fluid and ApoE genotyping were suggested for the diagnosis of AD, however, the result is either non-conclusive or with invasive procedure. Genome-wide association studies (GWASs) for AD suggested single nucleotide polymorphisms (SNPs) in many genes are associated with the risk of AD, but each only contributed with small effect to the disease. By incorporating a panel of established genetic susceptibility factors, the risk of an individual in getting AD could be better estimated. Further research will be required to reveal if adding to the current well-developed clinical diagnosis protocol, the accuracy and specificity of diagnosis of AD would be greatly improved and if this might also be beneficial in identifying pre-symptomatic AD patients for early diagnosis and intervention of the disease.

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Apolipoprotein-E genotyping in diagnosis of Alzheimer's disease

Cited by 39 publications

References 5 publications

Use of Genetic Variation as Biomarkers for Alzheimer's Disease

Use of Genetic Variation as Biomarkers for Alzheimer's Disease

Apolipoprotein E and ALzheimer's Disease: The Tip of the Susceptibility Iceberg

Panel of Genetic Variations as a Potential Non-invasive Biomarker for Early Diagnosis of Alzheimer's Disease

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