ArticleScience advances2021
Single-synapse analyses of Alzheimer's disease implicate pathologic tau, DJ1, CD47, and ApoE.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed.
- Early synaptic pathology is associated with small tau aggregates in Alzheimer's disease.Acta neuropathologica · 2026Article
- Article
- Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer's Disease? A Review of Recent Pertinent Observations from Molecular Biology.International journal of molecular sciences · 2025Review
- Mediterranean vs. Western diet effects on the primate cerebral cortical pre-synaptic proteome: Relationships with the transcriptome and multi-system phenotypes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Beyond cancer: The potential application of CD47-based therapy in non-cancer diseases.Acta pharmaceutica Sinica. B · 2025Review
- Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer's disease.Brain, behavior, and immunity · 2024Article
- Spatial Multi-Omics in Alzheimer's Disease: A Multi-Dimensional Approach to Understanding Pathology and Progression.Current issues in molecular biology · 2024Review
- The concept of resilience to Alzheimer's Disease: current definitions and cellular and molecular mechanisms.Molecular neurodegeneration · 2024Review
- STAMarker: determining spatial domain-specific variable genes with saliency maps in deep learning.Nucleic acids research · 2023Article
- Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models.The EMBO journal · 2023Article
- Cross-species comparative analysis of single presynapses.Scientific reports · 2023Article
- Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and informs causal proteins for Alzheimer's disease.Research square · 2023Article
- Alzheimer's disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression.Frontiers in synaptic neuroscience · 2023Review
- Single-cell spatial proteomic imaging for human neuropathology.Acta neuropathologica communications · 2022Article
- APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer's disease pathology and brain diseases.Molecular neurodegeneration · 2022Review
- Vesicular Glutamate Release from Feeder-FreehiPSC-Derived Neurons.International journal of molecular sciences · 2022Article
- Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice.Molecular psychiatry · 2022Article
- Application of Machine Learning Solutions to Optimize Parameter Prediction to Enhance Automatic NMR Metabolite Profiling.Metabolites · 2022Article
- Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling.Acta neuropathologica communications · 2022Article
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
Synaptic molecular characterization is limited for Alzheimer’s disease (AD). Our newly invented mass cytometry–based method, synaptometry by time of flight (SynTOF), was used to measure 38 antibody probes in approximately 17 million single-synapse events from human brains without pathologic change or with pure AD or Lewy body disease (LBD), nonhuman primates (NHPs), and PS/APP mice. Synaptic molecular integrity in humans and NHP was similar. Although not detected in human synapses, Aβ was in PS/APP mice single-synapse events. Clustering and pattern identification of human synapses showed expected disease-specific differences, like increased hippocampal pathologic tau in AD and reduced caudate dopamine transporter in LBD, and revealed previously unidentified findings including increased hippocampal CD47 and lowered DJ1 in AD and higher ApoE in AD with dementia. Our results were independently supported by multiplex ion beam imaging of intact tissue. This highlights the higher depth and breadth of insight on neurodegenerative diseases obtainable through SynTOF.
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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.