ArticleHuman molecular genetics2023
Genetic architecture of plasma Alzheimer disease biomarkers.
Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Genome-wide association analyses identify candidate loci for amyloid imaging and plasma biomarkers in adults with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Cross-ancestry genome-wide association study identifies implications of SORL1 in cerebral beta-amyloid deposition.Nature communications · 2025Pooled it
- Neurofilament Light Chain (NfL) in Neurodegenerative Diseases: Biological and Clinical Significance, Multi-Omics Integration, and AI-Driven Biomarker Modeling for Precision Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A multivariate approach to identify association between peripheral blood DNA methylation and cerebrospinal fluid biomarkers of Alzheimer disease.Scientific reports · 2025Article
- Associations of Longitudinal Changes in Blood Biomarkers of Dementia With the Proportion of Genetically Inferred African Ancestry.Neurology · 2025Article
- Genome-wide association of tau neuroimaging and plasma biomarkers in adults with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A genetic and proteomic comparison of key AD biomarkers across tissues.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Genetic and multi-omic resources for Alzheimer disease and related dementia from the Knight Alzheimer Disease Research Center.Scientific data · 2024Article
- Apolipoprotein E in Alzheimer's disease trajectories and the next-generation clinical care pathway.Nature neuroscience · 2024Review
- Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank.BMC medicine · 2024Article
- Pitfalls of predicting age-related traits by polygenic risk scores.Annals of human genetics · 2023Review
- Plasma biomarker trajectories: Impact of AD genetic risk and clinical progression.Alzheimer's & dementia (Amsterdam, Netherlands)Article
- The words community dwelling, Spanish-preferring Mexican/Mexican American adults use to talk about Alzheimer's disease and genetic testing: Implications for education and outreach.Alzheimer's & dementia (New York, N. Y.)Article
- Heritability of Alzheimer's disease-related plasma biomarkers in the Amish population.Alzheimer's & dementia (Amsterdam, Netherlands)Article
- Application of machine learning to blood-based biomarkers of Alzheimer's disease in Down syndrome.Alzheimer's & dementia (Amsterdam, Netherlands)Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Genome-wide association studies (GWAS) of cerebrospinal fluid (CSF) Alzheimer's Disease (AD) biomarker levels have identified novel genes implicated in disease risk, onset and progression. However, lumbar punctures have limited availability and may be perceived as invasive. Blood collection is readily available and well accepted, but it is not clear whether plasma biomarkers will be informative for genetic studies. Here we perform genetic analyses on concentrations of plasma amyloid-β peptides Aβ40 (n = 1,467) and Aβ42 (n = 1,484), Aβ42/40 (n = 1467) total tau (n = 504), tau phosphorylated (p-tau181; n = 1079) and neurofilament light (NfL; n = 2,058). GWAS and gene-based analysis was used to identify single variant and genes associated with plasma levels. Finally, polygenic risk score and summary statistics were used to investigate overlapping genetic architecture between plasma biomarkers, CSF biomarkers and AD risk. We found a total of six genome-wide significant signals. APOE was associated with plasma Aβ42, Aβ42/40, tau, p-tau181 and NfL. We proposed 10 candidate functional genes on the basis of 12 single nucleotide polymorphism-biomarker pairs and brain differential gene expression analysis. We found a significant genetic overlap between CSF and plasma biomarkers. We also demonstrate that it is possible to improve the specificity and sensitivity of these biomarkers, when genetic variants regulating protein levels are included in the model. This current study using plasma biomarker levels as quantitative traits can be critical to identification of novel genes that impact AD and more accurate interpretation of plasma biomarker levels.
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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.