ArticleMolecular & cellular proteomics : MCP2023
Integrated Proteomics to Understand the Role of Neuritin (NRN1) as a Mediator of Cognitive Resilience to Alzheimer's Disease.
Article in Molecular & cellular proteomics : MCP, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Asymptomatic Versus Symptomatic Alzheimer's Disease Neuropathology: A Systematic Review of Differences Reported in Post-Mortem Studies.Neuropathology and applied neurobiology · 2026Pooled it
- Local autophagy impairment triggers brain-wide presynaptic remodeling and resilience.The EMBO journal · 2026Article
- The Role of Neuritin 1 in Synaptic Plasticity and Sensory Nerve Function: Integrator of Neurotrophic, Metabolic and Injury Signals.The European journal of neuroscience · 2026Review
- A Multi-Network Approach Identifies Proteins Related to Dendritic Spines in Alzheimer's Disease.eNeuro · 2026Article
- Resilience to Endoplasmic Reticulum Stress Mitigates Membrane Hyperexcitability Underlying Late Disease Onset in a Murine Model of SCA6.Annals of neurology · 2026Article
- Verification of biological markers of subacute cutaneous lupus erythematosus via TMT labelling proteomics combined with transcriptome data.Annals of medicine · 2025Article
- Proteomic Insight Into Alzheimer's Disease Pathogenesis Pathways.Proteomics · 2025Review
- Interspecies Organoids Reveal Human-Specific Molecular Features of Dopaminergic Neuron Development and Vulnerability.bioRxiv : the preprint server for biology · 2025Article
- Proteomic landscape of Alzheimer's disease: emerging technologies, advances and insights (2021 - 2025).Molecular neurodegeneration · 2025Review
- A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer's disease.Nature medicine · 2025Article
- Synapse vulnerability and resilience underlying Alzheimer's disease.EBioMedicine · 2025Review
- Exome sequencing identifies genes for socioeconomic status in 350,770 individuals.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Stereo-seq of the prefrontal cortex in aging and Alzheimer's disease.Nature communications · 2025Article
- NRN1 may Modulate Tau Phosphorylation and Neuronal Apoptosis in ADCurrent Alzheimer research · 2025Article
- Neuritin: a multifaceted neuroprotective factor with emerging applications for neurodegeneration.Frontiers in neuroscience · 2025Review
- Large-scale deep proteomic analysis in Alzheimer's disease brain regions across race and ethnicity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Dendritic spine head diameter predicts episodic memory performance in older adults.Science advances · 2024Article
- Analysis and experimental validation of necroptosis-related molecular classification, immune signature and feature genes in Alzheimer's disease.Apoptosis : an international journal on programmed cell death · 2024Article
- Spatial Dissection of the Distinct Cellular Responses to Normal Aging and Alzheimer's Disease in Human Prefrontal Cortex at Single-Nucleus Resolution.medRxiv : the preprint server for health sciences · 2024Article
- Gene-expression profiling of individuals resilient to Alzheimer's disease reveals higher expression of genes related to metallothionein and mitochondrial processes and no changes in the unfolded protein response.Acta neuropathologica communications · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The molecular mechanisms and pathways enabling certain individuals to remain cognitively normal despite high levels of Alzheimer's disease (AD) pathology remain incompletely understood. These cognitively normal people with AD pathology are described as preclinical or asymptomatic AD (AsymAD) and appear to exhibit cognitive resilience to the clinical manifestations of AD dementia. Here we present a comprehensive network-based approach from cases clinically and pathologically defined as asymptomatic AD to map resilience-associated pathways and extend mechanistic validation. Multiplex tandem mass tag MS (TMT-MS) proteomic data (n = 7787 proteins) was generated on brain tissue from Brodmann area 6 and Brodmann area 37 (n = 109 cases, n = 218 total samples) and evaluated by consensus weighted gene correlation network analysis. Notably, neuritin (NRN1), a neurotrophic factor previously linked to cognitive resilience, was identified as a hub protein in a module associated with synaptic biology. To validate the function of NRN1 with regard to the neurobiology of AD, we conducted microscopy and physiology experiments in a cellular model of AD. NRN1 provided dendritic spine resilience against amyloid-β (Aβ) and blocked Aβ-induced neuronal hyperexcitability in cultured neurons. To better understand the molecular mechanisms of resilience to Aβ provided by NRN1, we assessed how exogenous NRN1 alters the proteome by TMT-MS (n = 8238 proteins) of cultured neurons and integrated the results with the AD brain network. This revealed overlapping synapse-related biology that linked NRN1-induced changes in cultured neurons with human pathways associated with cognitive resilience. Collectively, this highlights the utility of integrating the proteome from the human brain and model systems to advance our understanding of resilience-promoting mechanisms and prioritize therapeutic targets that mediate resilience to AD.
Indexed as
Identifiers
What OpenQuestion holds
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.