ArticleScience translational medicine2021
Cis P-tau underlies vascular contribution to cognitive impairment and dementia and can be effectively targeted by immunotherapy in mice.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 66 citations in OpenAlex.
- Review
- Endogenous neuroprotection in vascular cognitive impairment and dementia.EBioMedicine · 2026Review
- Passive immunotherapy targeting pathogenic tau restores neuronal structure and function following spinal cord injury.Spinal cord · 2026Article
- Eicosapentaenoic acid reprograms cerebrovascular metabolism and impairs repair after brain injury, with relevance to chronic traumatic encephalopathy.Cell reports · 2026Article
- Meningeal lymphatic architecture and drainage dynamics surrounding the human middle meningeal artery.iScience · 2025Article
- Article
- Immunization targeting diseased proteins in synucleinopathy and tauopathy: insights from clinical trials.Translational neurodegeneration · 2025Review
- Novel peptidomimetic compounds attenuate hypoxic-ischemic brain injury in neonatal rats.Experimental neurology · 2025Article
- Evolution of Alzheimer's Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy.Pharmaceutics · 2025Review
- Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia.Biomedicines · 2024Review
- Complex regulation of tau phosphorylation by the endothelin system in brain microvascular endothelial cells (BMVECs): link to barrier function.Clinical science (London, England : 1979) · 2024Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- Review
- Review
- p17/C18-ceramide-mediated mitophagy is an endogenous neuroprotective response in preclinical and clinical brain injury.PNAS nexus · 2024Article
- A nonhuman primate model with Alzheimer's disease-like pathology induced by hippocampal overexpression of human tau.Alzheimer's research & therapy · 2024Article
- Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease.Translational neurodegeneration · 2024Review
- Neuronal Vulnerability of the Entorhinal Cortex to Tau Pathology in Alzheimer's Disease.British journal of biomedical science · 2024Review
- The role of the Pin1-Frontiers in cell and developmental biology · 2024Review
- Tau Immunotherapies for Alzheimer's Disease and Related Tauopathies: Status of Trials and Insights from Preclinical Studies.Journal of Alzheimer's disease : JAD · 2024Review
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 3 countries.
Funding
Abstract
Compelling evidence supports vascular contributions to cognitive impairment and dementia (VCID) including Alzheimer's disease (AD), but the underlying pathogenic mechanisms and treatments are not fully understood. Cis P-tau is an early driver of neurodegeneration resulting from traumatic brain injury, but its role in VCID remains unclear. Here, we found robust cis P-tau despite no tau tangles in patients with VCID and in mice modeling key aspects of clinical VCID, likely because of the inhibition of its isomerase Pin1 by DAPK1. Elimination of cis P-tau in VCID mice using cis-targeted immunotherapy, brain-specific Pin1 overexpression, or DAPK1 knockout effectively rescues VCID-like neurodegeneration and cognitive impairment in executive function. Cis mAb also prevents and ameliorates progression of AD-like neurodegeneration and memory loss in mice. Furthermore, single-cell RNA sequencing revealed that young VCID mice display diverse cortical cell type-specific transcriptomic changes resembling old patients with AD, and the vast majority of these global changes were recovered by cis-targeted immunotherapy. Moreover, purified soluble cis P-tau was sufficient to induce progressive neurodegeneration and brain dysfunction by causing axonopathy and conserved transcriptomic signature found in VCID mice and patients with AD with early pathology. Thus, cis P-tau might play a major role in mediating VCID and AD, and antibody targeting it may be useful for early diagnosis, prevention, and treatment of cognitive impairment and dementia after neurovascular insults and in AD.
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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.