ArticlePloS one2021
Molecular subtyping of Alzheimer's disease with consensus non-negative matrix factorization.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Network dynamics-based subtyping of Alzheimer's disease with microglial genetic risk factors.Alzheimer's research & therapy · 2024Article
- In vivo validation of late-onset Alzheimer's disease genetic risk factors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Multilayer Analysis of RNA Sequencing Data in Alzheimer's Disease to Unravel Molecular Mysteries.Advances in neurobiology · 2024Review
- Article
- Artificial intelligence for biomarker discovery in Alzheimer's disease and dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Unbiased classification of the elderly human brain proteome resolves distinct clinical and pathophysiological subtypes of cognitive impairment.Neurobiology of disease · 2023Article
- How Many Alzheimer-Perusini's Atypical Forms Do We Still Have to Discover?Biomedicines · 2023Review
- Identification of the Subtypes of Renal Ischemia-Reperfusion Injury Based on Pyroptosis-Related Genes.Biomolecules · 2023Article
- Heterogeneity of Alzheimer's disease identified by neuropsychological test profiling.PloS one · 2023Article
- Multi-omic integration via similarity network fusion to detect molecular subtypes of ageing.Brain communications · 2023Article
- Recent update on the heterogeneity of the Alzheimer's disease spectrum.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a heterogeneous disease and exhibits diverse clinical presentations and disease progression. Some pathological and anatomical subtypes have been proposed. However, these subtypes provide a limited mechanistic understanding for AD. Leveraging gene expression data of 222 AD patients from The Religious Orders Study and Memory and Aging Project (ROSMAP) Study, we identified two AD molecular subtypes (synaptic type and inflammatory type) using consensus non-negative matrix factorization (NMF). Synaptic type is characterized by disrupted synaptic vesicle priming and recycling and synaptic plasticity. Inflammatory type is characterized by disrupted IL2, interferon alpha and gamma pathways. The two AD molecular subtypes were validated using independent data from Gene Expression Omnibus. We further demonstrated that the two molecular subtypes are associated with APOE genotypes, with synaptic type more prevalent in AD patients with E3E4 genotype and inflammatory type more prevalent in AD patients with E3E3 genotype (p = 0.031). In addition, two molecular subtypes are differentially represented in male and female AD, with synaptic type more prevalent in male and inflammatory type in female patients (p = 0.051). Identification of AD molecular subtypes has potential in facilitating disease mechanism understanding, clinical trial design, drug discovery, and precision medicine for AD.
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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.