ArticleAlzheimer's & dementia (New York, N. Y.)2016
A Genetics-based Biomarker Risk Algorithm for Predicting Risk of Alzheimer's Disease.
Article in Alzheimer's & dementia (New York, N. Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
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- A transcriptome-wide association study identifies novel blood-based gene biomarker candidates for Alzheimer's disease risk.Human molecular genetics · 2021Article
- A cross-sectional study in healthy elderly subjects aimed at development of an algorithm to increase identification of Alzheimer pathology for the purpose of clinical trial participation.Alzheimer's research & therapy · 2021Article
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- The APOE gene cluster responds to air pollution factors in mice with coordinated expression of genes that differs by age in humans.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Consequences of Metabolic Disruption in Alzheimer's Disease Pathology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Gene-environment interactions in Alzheimer's disease: A potential path to precision medicine.Pharmacology & therapeutics · 2019Review
- The TOMMORROW study: Design of an Alzheimer's disease delay-of-onset clinical trial.Alzheimer's & dementia (New York, N. Y.) · 2019Article
- Haplotype analysis of APOE intragenic SNPs.BMC neuroscience · 2018Article
- The biological foundation of the genetic association of TOMM40 with late-onset Alzheimer's disease.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
- Characterization ofAlzheimer's & dementia (New York, N. Y.) · 2017Article
- ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease.Trends in endocrinology and metabolism: TEM · 2017Review
- Towards precision medicine in Alzheimer's disease: deciphering genetic data to establish informative biomarkers.Expert review of precision medicine and drug development · 2017Article
- How can we really improve screening methods for AD prevention trials?Alzheimer's & dementia (New York, N. Y.) · 2016Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundA straightforward, reproducible blood-based test that predicts age dependent risk of Alzheimer's disease (AD) could be used as an enrichment tool for clinical development of therapies. This study evaluated the prognostic performance of a genetics-based biomarker risk algorithm (GBRA) established on a combination of Apolipoprotein E (APOE)/Translocase of outer mitochondrial membrane 40 homolog (TOMM40) genotypes and age, then compare it to cerebrospinal fluid (CSF) biomarkers, neuroimaging and neurocognitive tests using data from two independent AD cohorts.
methodsThe GBRA was developed using data from the prospective Bryan-ADRC study (n=407; 86 conversion events (mild cognitive impairment (MCI) or late onset Alzheimer's disease (LOAD)). The performance of the algorithm was tested using data from the ADNI study (n=660; 457 individuals categorized as MCI or LOAD).
resultsThe positive predictive values (PPV) and negative predictive values (NPV) of the GBRA are in the range of 70-80%. The relatively high odds ratio (approximately 3-5) and significant net reclassification index (NRI) scores comparing the GBRA to a version based on APOE and age alone support the value of the GBRA in risk prediction for MCI due to LOAD. Performance of the GBRA compares favorably with CSF and imaging (fMRI) biomarkers. In addition, the GBRA "high" and "low" AD-risk categorizations correlated well with pathological CSF biomarker levels, PET amyloid burden and neurocognitive scores.
conclusionsUnlike dynamic markers (i.e., imaging, protein or lipid markers) that may be influenced by factors unrelated to disease, genomic DNA is easily collected, stable, and the technical methods for measurement are robust, inexpensive, and widely available. The performance characteristics of the GBRA support its use as a pharmacogenetic enrichment tool for LOAD delay of onset clinical trials, and merits further evaluation for its clinical utility in evaluating therapeutic efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.