ArticleAlzheimer's research & therapy2020
CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer's disease.
Article in Alzheimer's research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Associations between cerebrospinal fluid markers and cognition in ageing and dementia: A systematic review.The European journal of neuroscience · 2022Pooled it
- Orexins and neuregulins as exemplars of peptide physiology in the brain: experimental challenges and implications for neuropathology.Frontiers in cellular neuroscience · 2026Article
- Multiple Roles for Neuregulins and Their v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog Receptors in Neurodegenerative Disease Pathogenesis and Therapy.The American journal of pathology · 2025Review
- Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model.Journal of neuroinflammation · 2025Article
- Identification of MicroRNA Drug Targets for Alzheimer's and Diabetes Mellitus Using Network Medicine.Current Alzheimer research · 2025Article
- MALT1 in cerebrospinal fluid: a prognostic biomarker and potential therapeutic target in Alzheimer's disease.Frontiers in neurology · 2025Article
- Plasma vesicle-associated membrane protein 2 and glial fibrillary acidic protein associate with synaptic density in older adults without dementia.Brain communications · 2025Article
- Exercise to Counteract Alzheimer's Disease: What Do Fluid Biomarkers Say?International journal of molecular sciences · 2024Review
- Impairments of GABAergic transmission in hippocampus mediate increased susceptibility of epilepsy in the early stage of Alzheimer's disease.Cell communication and signaling : CCS · 2024Article
- Biofluid biomarkers for Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- Article
- Fine-grained cell-type specific association studies with human bulk brain data using a large single-nucleus RNA sequencing based reference panel.Scientific reports · 2023Article
- Identification of novel biomarkers linking depressive disorder and Alzheimer's disease based on an integrative bioinformatics analysis.BMC genomic data · 2023Article
- AD-Syn-Net: systematic identification of Alzheimer's disease-associated mutation and co-mutation vulnerabilities via deep learning.Briefings in bioinformatics · 2023Article
- The Key Role of Magnetic Resonance Imaging in the Detection of Neurodegenerative Diseases-Associated Biomarkers: A Review.Molecular neurobiology · 2022Review
- Plasma neuregulin 1 as a synaptic biomarker in Alzheimer's disease: a discovery cohort study.Alzheimer's research & therapy · 2022Article
- Bioinformatics Analysis of Publicly Available Single-Nuclei Transcriptomics Alzheimer's Disease Datasets RevealsFrontiers in aging neuroscience · 2022Article
- Neuregulin 1 Gene (Cancers · 2021Review
- Body Fluid Biomarkers for Alzheimer's Disease-An Up-To-Date Overview.Biomedicines · 2020Review
- Increased Levels of Serum Neuregulin 1 Associated with Cognitive Impairment in Vascular Dementia.BioMed research international · 2020Article
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Authors and funding
11 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe presynaptic protein neuregulin1 (NRG1) is cleaved by beta-site APP cleaving enzyme 1 (BACE1) in a similar way as amyloid precursor protein (APP) NRG1 can activate post-synaptic receptor tyrosine-protein kinase erbB4 (ErbB4) and was linked to schizophrenia. The NRG1/ErbB4 complex is neuroprotective, can trigger synaptogenesis and plasticity, increases the expression of NMDA and GABA receptors, and can induce neuroinflammation. This complex can reduce memory formation. In Alzheimer's disease (AD) brains, NRG1 accumulates in neuritic plaques. It is difficult to determine if NRG1 has beneficial and/or detrimental effects in AD. BACE1 levels are increased in AD brains and cerebrospinal fluid (CSF) and may lead to enhanced NRG1 secretion, but no study has assessed CSF NRG1 levels in AD and mild cognitive impairment (MCI) patients.
methodsThis retrospective study included 162 patients suffering from AD dementia (54), MCI with progression to AD dementia (MCI-AD) (27), non-AD MCI (30), non-AD dementias (30), and neurological controls (27). All patients had neurological examinations, brain MRI, and neuropsychological evaluations. After written informed consent and using enzyme-linked immunosorbent assays (ELISAs), CSF samples were evaluated for Aβ1-42, Aβ1-40, total tau (T-tau), phosphorylated tau on threonine 181 (P-tau), BACE1, growth-associated protein 43 (GAP 43), neurogranin (Ng), and NRG1.
resultsLevels of NRG1 were significantly increased in the CSF of AD (+ 36%) and MCI-AD (+ 28%) patients compared to neurological controls and also non-AD MCI and non-AD dementias. In addition, in AD and MCI-AD patients, NRG1 levels positively correlated with Aβ1-42 but not with T-tau, P-tau, and BACE1 levels and negatively correlated with MMSE scores. A longitudinal follow-up study of AD patients revealed a trend (p = 0.08) between CSF NRG1 levels and cognitive decline. In the overall population, NRG1 correlated with MMSE and the synaptic biomarkers GAP 43 and neurogranin.
conclusionsOur results showed that CSF NRG1 levels are increased in AD and MCI-AD as compared to controls and other dementias. CSF NRG1 levels are associated with cognitive evolution, and a major outcome of our findings is that synaptic NRG1 could be involved in the pathophysiology of AD. Modulating brain NRG1 activity may represent a new therapeutic target in AD.
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