ArticleBrain : a journal of neurology2022
The role of mTORC1 activation in seizure-induced exacerbation of Alzheimer's disease.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Duration-dependent hippocampal structural changes in focal epilepsy: multicenter neuroimaging evidence.Journal of translational medicine · 2026Article
- Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review).International journal of molecular medicine · 2026Review
- Epilepsy and Alzheimer Disease: Epidemiologic, Clinical, Molecular, and Neuropathologic Convergences and Divergences.Neurology. Clinical practice · 2026Review
- Seizures drive tau propagation in a tauopathy mouse model.bioRxiv : the preprint server for biology · 2026Article
- RLIP76: a versatile ATP-dependent transporter as a pharmacotherapeutic target for epilepsy management.Inflammopharmacology · 2026Review
- Article
- Epilepsy in the Aging Brain: Time to Rethink the Narrative.Epilepsy currents · 2026Article
- The impact of long-term antiseizure treatment on cognitive decline in late-onset epileptic prodromal Alzheimer's disease: an exploratory study.Frontiers in aging neuroscience · 2026Article
- ZCCHC17: a target for synaptic dysfunction and neuronal excitability in Alzheimer's disease.Frontiers in aging neuroscience · 2026Review
- Screening antiseizure medications to break the cycle between neuronal hyperexcitability and Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- Sex-specific proteomic analysis of epileptic brain tissues from Pten knockout mice and human refractory epilepsy.Experimental neurology · 2025Article
- Hyperactive neuronal networks enhance tau spread in an Alzheimer's disease mouse model.bioRxiv : the preprint server for biology · 2025Article
- The association of seizure control with neuropathology in dementia.Brain : a journal of neurology · 2025Article
- Microglial MS4A4A Protects against Epileptic Seizures in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neurodegeneration and the immune system: lessons from autoimmune encephalitis.Journal of neurology · 2025Review
- The Bidirectional Relationship Between Epilepsy and Alzheimer's Disease.Current neurology and neuroscience reports · 2025Review
- Cellular senescence in Alzheimer's disease: from physiology to pathology.Translational neurodegeneration · 2024Review
- Factors Affecting Resilience and Prevention of Alzheimer's Disease and Related Dementias.Annals of neurology · 2024Review
- Alzheimer's Disease and Epilepsy: Exploring Shared Pathways and Promising Biomarkers for Future Treatments.Journal of clinical medicine · 2024Review
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10 authors at 3 institutions in 1 country.
Funding
Abstract
The risk of seizures is 10-fold higher in patients with Alzheimer's disease than the general population, yet the mechanisms underlying this susceptibility and the effects of these seizures are poorly understood. To elucidate the proposed bidirectional relationship between Alzheimer's disease and seizures, we studied human brain samples (n = 34) from patients with Alzheimer's disease and found that those with a history of seizures (n = 14) had increased amyloid-β and tau pathology, with upregulation of the mechanistic target of rapamycin (mTOR) pathway, compared with patients without a known history of seizures (n = 20). To establish whether seizures accelerate the progression of Alzheimer's disease, we induced chronic hyperexcitability in the five times familial Alzheimer's disease mouse model by kindling with the chemoconvulsant pentylenetetrazol and observed that the mouse model exhibited more severe seizures than the wild-type. Furthermore, kindled seizures exacerbated later cognitive impairment, Alzheimer's disease neuropathology and mTOR complex 1 activation. Finally, we demonstrated that the administration of the mTOR inhibitor rapamycin following kindled seizures rescued enhanced remote and long-term memory deficits associated with earlier kindling and prevented seizure-induced increases in Alzheimer's disease neuropathology. These data demonstrated an important link between chronic hyperexcitability and progressive Alzheimer's disease pathology and suggest a mechanism whereby rapamycin may serve as an adjunct therapy to attenuate progression of the disease.
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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.