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Molecular subtyping of Alzheimer’s disease with consensus non-negative matrix factorization
- Source :
- PLoS ONE, PLoS ONE, Vol 16, Iss 5, p e0250278 (2021)
- Publication Year :
- 2021
- Publisher :
- Public Library of Science, 2021.
-
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.
- Subjects :
- Apolipoprotein E
Male
Physiology
Gene Expression
Genome-wide association study
Disease
Bioinformatics
Alzheimer's Disease
Nervous System
Medical Conditions
Gene Frequency
Genotype
Medicine and Health Sciences
Prevalence
Immune Response
Cognitive Impairment
Aged, 80 and over
Multidisciplinary
Cognitive Neurology
Age Factors
Neurodegenerative Diseases
Genomics
Middle Aged
Subtyping
Electrophysiology
Neurology
Medicine
Female
Synaptic Vesicles
Anatomy
Cellular Structures and Organelles
Synaptic vesicle priming
Metabolic Networks and Pathways
Research Article
Science
Inflammatory Diseases
Cognitive Neuroscience
Immunology
Alpha interferon
Neurophysiology
Biology
Signs and Symptoms
Apolipoproteins E
Sex Factors
Alzheimer Disease
Mental Health and Psychiatry
Genetics
Genome-Wide Association Studies
Humans
Vesicles
Aged
Inflammation
Models, Statistical
Biology and Life Sciences
Computational Biology
Human Genetics
Cell Biology
Genome Analysis
Synaptic plasticity
Synapses
Cognitive Science
Interleukin-2
Dementia
Interferons
Clinical Medicine
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 16
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....de23f11e13c4659c99f3054a039663ea