ArticleNature neuroscience2020
Tau induces PSD95-neuronal NOS uncoupling and neurovascular dysfunction independent of neurodegeneration.
Article in Nature neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 122 citations in OpenAlex.
- The Effect of a Neuronal Nitric Oxide Synthase Inhibitor on Neurovascular Regulation in Humans.Circulation research · 2022Trial
- Neuronal nitric oxide synthase regulates regional brain perfusion in healthy humans.Cardiovascular research · 2022Trial
- Intranasal Insulin Reduces White Matter Hyperintensity Progression in Association with Improvements in Cognition and CSF Biomarker Profiles in Mild Cognitive Impairment and Alzheimer's Disease.The journal of prevention of Alzheimer's disease · on this mapTrial
- Functional and structural characterization of dendritic spine pathology in a mouse model of tauopathy.iScience · 2026Article
- LncRNA Gas5, a Target of the Nonsense-Mediated Decay Pathway in the Brain, Regulates Neuroinflammation and Neurodegenerative Disease Pathways in a Tauopathy Mouse Model.International journal of molecular sciences · 2026Article
- Tau protein differentially affects Piezo1 and Kir2.1 channels in brain capillary endothelial cells.Biophysical journal · 2026Article
- Frontotemporal dementia associated CHCHD10Cell death & disease · 2026Article
- ZL006 Treatment Reduces Inflammation, Oxidative Stress, and Brain AβInternational journal of molecular sciences · 2026Article
- Neurovascular Uncoupling in Alzheimer's and Parkinson's Diseases: Mechanisms and Therapeutic Strategies.Brain sciences · 2026Review
- Microvascular dysfunction and aberrant network activity drive reduced brain oxygenation in a mouse tauopathy model.Research square · 2025Article
- Cerebrovascular p16Acta neuropathologica communications · 2025Article
- The Role and Pathogenesis of Tau Protein in Alzheimer's Disease.Biomolecules · 2025Review
- Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025Review
- Molecular and cellular characteristics of cerebrovascular cell types and their contribution to neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39.Nature communications · 2025Article
- The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation.Alzheimer's research & therapy · 2025Article
- Cerebrovascular alterations in a mouse model of late-onset Alzheimer's disease.Neurophotonics · 2025Article
- Increased frontocortical microvascular raspberry density in frontotemporal lobar degeneration compared to Lewy body disease and control cases: a neuropathological study.Free neuropathology · 2025Article
- The pathophysiology of mixed Alzheimer's disease and vascular dementia.Theranostics · 2025Review
- Depth-dependent contributions of various vascular zones to cerebral autoregulation and functional hyperemia: An in-silico analysis.PloS one · 2025Article
14 more citing papers are in PubMed but not listed here.
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15 authors at 1 institution in 1 country.
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Abstract
Cerebrovascular abnormalities have emerged as a preclinical manifestation of Alzheimer's disease and frontotemporal dementia, diseases characterized by the accumulation of hyperphosphorylated forms of the microtubule-associated protein tau. However, it is unclear whether tau contributes to these neurovascular alterations independent of neurodegeneration. We report that mice expressing mutated tau exhibit a selective suppression of neural activity-induced cerebral blood flow increases that precedes tau pathology and cognitive impairment. This dysfunction is attributable to a reduced vasodilatation of intracerebral arterioles and is reversible by reducing tau production. Mechanistically, the failure of neurovascular coupling involves a tau-induced dissociation of neuronal nitric oxide synthase (nNOS) from postsynaptic density 95 (PSD95) and a reduced production of the potent vasodilator nitric oxide during glutamatergic synaptic activity. These data identify glutamatergic signaling dysfunction and nitric oxide deficiency as yet-undescribed early manifestations of tau pathobiology, independent of neurodegeneration, and provide a mechanism for the neurovascular alterations observed in the preclinical stages of tauopathies.
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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.