Seizure resistance without parkinsonism in aged mice after tau reduction
Open accessAbstract
Tau is an emerging target for Alzheimer's disease (AD) and other conditions with epileptiform activity. Genetic tau reduction (in Tau(+/-) and Tau(-/-) mice) prevents deficits in AD models and has an excitoprotective effect, increasing resistance to seizures, without causing apparent neuronal dysfunction. However, most studies of tau reduction have been conducted in <1-year-old mice, and the effects of tau reduction in aged mice are less clear. Specifically, whether the excitoprotective effects of tau reduction persist with aging is unknown and whether tau reduction causes neuronal dysfunction, including parkinsonism, with aging is controversial. Here, we performed a comprehensive analysis of 2-year-old Tau(+/+), Tau(+/-), and Tau(-/-) mice. In aged mice, tau reduction still conferred resistance to pentylenetetrazole-induced seizures. Moreover, tau reduction did not cause parkinsonian abnormalities in dopamine levels or motor function and did not cause iron accumulation or impaired cognition, although Tau(-/-) mice had mild hyperactivity and decreased brain weight. Importantly, the excitoprotective effect in aged Tau(+/-) mice was not accompanied by detectable abnormalities, indicating that partially reducing tau or blocking its function may be a safe and effective therapeutic approach for AD and other conditions with increased excitability.
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Some data suggest that Aβ toxicity is partially mediated through tau, as tau knockout mice are protected against Aβ-induced insults including cognitive effects, seizures, survival, axonal transport, and DNA double-stranded breaks.
“Some data suggest that Aβ toxicity is partially mediated through tau (50–52) as the tau knockout mouse has proven to be protected against a growing number of Aβ-induced insults, including those affecting cognition (50, 53), seizures (14, 50, 51, 54, 55), survival (50, 51, 54), axonal transport (52), and double-stranded breaks in DNA (55).”
From Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy (2017) · cites this paper as [14]
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- Authors
- Li, Z., Hall, A. M., Kelinske, M., & Roberson, E. D.
- Affiliations
- University of Alabama at Birmingham (US)
- Southern Research Institute (US)
- Corresponding author
- Roberson, Erik D.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 35
- Issue
- 11
- Pages
- 2617-2624
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4171213
- OpenAlex
- W2076333797
- Cited by
- 71
- References
- 22
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 3
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01NS075487)
- BrightFocus Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau protein, Alzheimer's disease, seizure resistance, pentylenetetrazole-induced seizures, parkinsonism, aging, neuronal dysfunction, dopamine, iron accumulation, cognitive impairment, hyperactivity, brain weight
- MeSH terms
- Aging, Alzheimer Disease, Animals, Mice, Inbred C57BL, Seizures, tau Proteins, Mice, Knockout, Parkinsonian Disorders, Molecular Targeted Therapy
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