ArticleNeurochemical research2016
Caspase-3-Dependent Proteolytic Cleavage of Tau Causes Neurofibrillary Tangles and Results in Cognitive Impairment During Normal Aging.
Article in Neurochemical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Blood measure of neuronal death is exponentially higher with age, especially in females, and halted in Alzheimer's disease by GM-CSF treatment.Cell reports. Medicine · 2026Article
- Cyclophilin D (CypD) ablation prevents neurodegeneration and cognitive damage induced by caspase-3 cleaved tau.Free radical biology & medicine · 2025Article
- Long-term exposure to excessive norepinephrine in the brain induces tau aggregation, neuronal death, and cognitive deficits in early tau transgenic mice.Aging cell · 2025Article
- Caspases in Alzheimer's Disease: Mechanism of Activation, Role, and Potential Treatment.Molecular neurobiology · 2024Review
- Identification of high-performing antibodies for the reliable detection of Tau proteoforms by Western blotting and immunohistochemistry.Acta neuropathologica · 2024Article
- Exploring the significance of caspase-cleaved tau in tauopathies and as a complementary pathology to phospho-tau in Alzheimer's disease: implications for biomarker development and therapeutic targeting.Acta neuropathologica communications · 2024Review
- Abnormal protein post-translational modifications induces aggregation and abnormal deposition of protein, mediating neurodegenerative diseases.Cell & bioscience · 2024Review
- Pathological Impact of Tau Proteolytical Process on Neuronal and Mitochondrial Function: a Crucial Role in Alzheimer's Disease.Molecular neurobiology · 2023Review
- Quetiapine Moderates Doxorubicin-Induced Cognitive Deficits: Influence of Oxidative Stress, Neuroinflammation, and Cellular Apoptosis.International journal of molecular sciences · 2023Article
- Activity-dependent tau cleavage by caspase-3 promotes neuronal dysfunction and synaptotoxicity.iScience · 2023Article
- In Vitro Antiviral Effect and Potential Neuroprotection ofPharmaceuticals (Basel, Switzerland) · 2023Article
- Aggregation of Disordered Proteins Associated with Neurodegeneration.International journal of molecular sciences · 2023Review
- Brain-aging related protein expression and imaging characteristics of mice exposed to chronic hypoxia at high altitude.Frontiers in aging neuroscience · 2023Article
- The "mitochondrial stress responses": the "Dr. Jekyll and Mr. Hyde" of neuronal disorders.Neural regeneration research · 2022Review
- Caspase-cleaved tau is senescence-associated and induces a toxic gain of function by putting a brake on axonal transport.Molecular psychiatry · 2022Article
- Unconventional secretion of tau by VAMP8 impacts its intra- and extracellular cleavage.Frontiers in cell and developmental biology · 2022Article
- STOP Codon Mutations at Sites of Natural Caspase Cleavage Are Implicated in Autism and Alzheimer's Disease: The Case of ADNP.Frontiers in endocrinology · 2022Article
- FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model.NPJ aging and mechanisms of disease · 2021Article
- Alzheimer's Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia.International journal of molecular sciences · 2021Review
- Amelioration of oxidative stress and neuroinflammation in lipopolysaccharide-induced memory impairment using Rosmarinic acid in mice.Metabolic brain disease · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Mouse models of neurodegenerative diseases such as Alzheimer's disease (AD) are important for understanding how pathological signaling cascades change neural circuitry and with time interrupt cognitive function. Here, we introduce a non-genetic preclinical model for aging and show that it exhibits cleaved tau protein, active caspases and neurofibrillary tangles, hallmarks of AD, causing behavioral deficits measuring cognitive impairment. To our knowledge this is the first report of a non-transgenic, non-interventional mouse model displaying structural, functional and molecular aging deficits associated with AD and other tauopathies in humans with potentially high impact on both new basic research into pathogenic mechanisms and new translational research efforts. Tau aggregation is a hallmark of tauopathies, including AD. Recent studies have indicated that cleavage of tau plays an important role in both tau aggregation and disease. In this study we use wild type mice as a model for normal aging and resulting age-related cognitive impairment. We provide evidence that aged mice have increased levels of activated caspases, which significantly correlates with increased levels of truncated tau and formation of neurofibrillary tangles. In addition, cognitive decline was significantly correlated with increased levels of caspase activity and tau truncated by caspase-3. Experimentally induced inhibition of caspases prevented this proteolytic cleavage of tau and the associated formation of neurofibrillary tangles. Our study shows the strength of using a non-transgenic model to study structure, function and molecular mechanisms in aging and age related diseases of the brain.
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