Integrated Metabolomics and Transcriptomics Analysis Identifies Molecular Subtypes within the Early and Late Mild Cognitive Impairment Stages of Alzheimer's Disease
Yadav, S.; Zhou, S.; Karas, Z.; Zhang, Y.; Garmire, L. X.; ADNI Consortium,
Show abstract
Alzheimers disease (AD) is a heterogeneous neurodegenerative condition. This study identifies clinically relevant new molecular subtypes of the early and late mild cognitive impairment (EMCI and LMCI) stages of AD from 401 patients in the ADNI consortium. Metabolomics and peripheral blood mononuclear cell (PBMC) transcriptomics data are integrated using Similarity Network Fusion (SNF), resulting in two molecular subtypes within EMCI (EMCI-1 and EMCI-2) and LMCI (LMCI-1 and LMCI-2), respectively. Metabolomics, rather than gene expression profiling, is the major contributor to subtyping. Subtype-specific differences in metabolite levels and gene expression correlate with AD pathophysiology, supported by cognitive scores, pseudo-trajectory analysis, and longitudinal dementia diagnoses. The new molecular subtypes are further validated through the EFIGA dataset, and present a clear trend of increase in protein biomarkers including p-Tau181, p-Tau217, A{beta}40, and A{beta}42. These refined subtypes represent a step toward more personalized therapeutic strategies targeting early disease stages before AD diagnosis.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The ratio of plasma pTau181 and pTau217 to Aβ42 outperforms individual measurements in detecting brain amyloidosis 94%
- Prediction of brain age using structural magnetic resonance imaging: A comparison of clinical validity of publicly available software packages 93%
- Adherence to Life’s Essential 8 is associated with delayed white matter aging 92%
Similar papers in this journal
- A public resource of single cell transcriptomes and multiscale networks from persons with and without Alzheimer's disease 96%
- Deep clinical phenotyping of Alzheimer’s Disease Patients Leveraging Electronic Medical Records Data Identifies Sex-Specific Clinical Associations 96%
- Individual bioenergetic capacity as a potential source of resilience to Alzheimer’s disease 95%
Similar papers in this journal
- Manifestations of genetic risk for Alzheimer's Disease in the blood: a cross-sectional multi-omic analysis in healthy adults aged 18-90+ 96%
- Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer's disease-associated metabolites 94%
- Peripheral inflammation is associated with structural brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer's disease 94%
Similar papers in this journal
- Association of RDoC dimensions with post-mortem brain transcriptional profiles in Alzheimer’s Disease 96%
- Blood metabolites predicting Mild Cognitive Impairment in the Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL) 95%
- Machine learning methods applied to genotyping data capture interactions between single nucleotide variants in late onset Alzheimer’s disease 94%