Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models

Sánchez, Marina P.; García-Cabrero, Ana M.; Sánchez-Elexpuru, Gentzane; Burgos, Daniel F; Serratosa, Joan

doi:10.3390/ijms19041092

Cited by 54 publications

(53 citation statements)

References 208 publications

(283 reference statements)

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“…approximately 0.7%), while the highest frequency has been observed in PPA, of which the non-fluent type is mainly related to tau deposition. This is in agreement with recent literature data highlighting the role of tau protein in increasing seizure susceptibility and aberrant network excitability[4,44].389A novel finding of the present study is that epilepsy 390 in AD dementia seems to be more drug-responsive391 than epilepsy in non-AD dementias. As discussed 392 before, this result must be taken with caution consid-393 ering the limited number of subjects.…”

supporting

confidence: 91%

“…Thus, the role of tau protein seems relevant in determining the increased risk of epilepsy [44]. Indeed, tau pathology is present in AD, but it may also be present in FTD and DLB [44]. The results of the present study seem to suggest a preponderant role of tau protein among all misfolded ones.…”

Section: Discussionsupporting

confidence: 48%

“…Moreover, in non-demented patients suffering from refractory temporal lobe epilepsy, the presence of tau pathology has been related cognitive decline [43]. Thus, the role of tau protein seems relevant in determining the increased risk of epilepsy [44]. Indeed, tau pathology is present in AD, but it may also be present in FTD and DLB [44].…”

Section: Discussionmentioning

confidence: 99%

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Epilepsy in Neurodegenerative Dementias: A Clinical, Epidemiological, and EEG Study

Arnaldi

Donniaquio

Mattioli

et al. 2020

JAD

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Background: Seizures are common in patients with dementia but precise epidemiologic data of epilepsy in neurodegenerative dementia is lacking. Objective: The first aim of the study was to investigate prevalence and clinical characteristics of epilepsy in a large cohort of patients with neurodegenerative dementias. Subsequently, we explored clinical, neuropsychological, and quantitative electroencephalogram (qEEG) data of Alzheimer's disease (AD) patients with epilepsy (AD-EPI) as compared to AD patients without epilepsy (AD-CTR). Methods: We retrospectively evaluated consecutive patients with a diagnosis of a neurodegenerative dementia and a clinically diagnosed epilepsy that required antiepileptic drugs (AED). All patients underwent baseline comprehensive neuropsychological assessment. A follow-up of at least one year was requested to confirm the dementia diagnosis. In AD patients, qEEG power band analysis was performed. AD-CTR and AD-EPI patients were matched for age, Mini-Mental State Examination score, and gender. Results: Thirty-eight out of 2,054 neurodegenerative dementia patients had epilepsy requiring AED. The prevalence of epilepsy was 1.82% for AD, 1.28% for the behavioral variant of frontotemporal dementia (bvFTD), 2.47% for dementia with Lewy bodies (DLB), and 12% for primary progressive aphasia. Epilepsy were more drug-responsive in AD than in non-AD dementias. Finally, no significant differences were found in neuropsychological and qEEG data between AD-EPI and AD-CTR patients. Conclusion: In our cohort, AD, FTD, and DLB dementias have similar prevalence of epilepsy, even if AD patients were more responsive to AED. Moreover, AD-EPI patients did not have significant clinical, neuropsychological qEEG differences compared with AD-CTR patients.

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supporting

confidence: 91%

Section: Discussionsupporting

confidence: 48%

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Epilepsy in Neurodegenerative Dementias: A Clinical, Epidemiological, and EEG Study

Arnaldi

Donniaquio

Mattioli

et al. 2020

JAD

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“…Abnormalities in the expression and phosphorylation of tau have also been described in stroke, epilepsy, Alzheimer's disease, frontotemporal dementia, and chronic traumatic encephalopathies . In clinical situations, pathological deposition of hyperphosphorylated tau has been observed in brain samples obtained from surgical resection of epileptic tissue from patients with drug‐resistant chronic TLE . Similarly, brain tissue from other drug‐resistant epileptic conditions such as focal cortical dysplasia also displays hyperphosphorylated tau .…”

Section: Tau‐based Mechanisms In Epilepsymentioning

confidence: 99%

Neurodegenerative pathways as targets for acquired epilepsy therapy development

2020

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There is a growing body of clinical and experimental evidence that neurodegenerative diseases and epileptogenesis after an acquired brain insult may share common etiological mechanisms. Acquired epilepsy commonly develops as a comorbid condition in patients with neurodegenerative diseases such as Alzheimer's disease, although it is likely much under diagnosed in practice. Progressive neurodegeneration has also been described after traumatic brain injury, stroke, and other forms of brain insults. Moreover, recent evidence has shown that acquired epilepsy is often a progressive disorder that is associated with the development of drug resistance, cognitive decline, and worsening of other neuropsychiatric comorbidities. Therefore, new pharmacological therapies that target neurobiological pathways that underpin neurodegenerative diseases have potential to have both an anti-epileptogenic and diseasemodifying effect on the seizures in patients with acquired epilepsy, and also mitigate the progressive neurocognitive and neuropsychiatric comorbidities. Here, we review the neurodegenerative pathways that are plausible targets for the development of novel therapies that could prevent the development or modify the progression of acquired epilepsy, and the supporting published experimental and clinical evidence. K E Y W O R D SAMPA, amyloid-β, glutamate, mTOR, neuroinflammation, tau

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“…Interestingly, the efficacy of various antiepileptic drugs (AEDs) has been tested in epilepsy experimental models and in AD patients, showing a promising function in cognitive impairment prevention (Sánchez et al, 2018). Since tau hyperphosphorylation is the main mechanism responsible for NFT formation, it has been suggested that inhibiting different tau kinases such as CDK5 and GSK3β, involved in tau hyperphosphorylation, could reduce their aggregation (Xie et al, 2017;Holzer et al, 2018), observed in AD (Morris et al, 2011) and epilepsy (Sen et al, 2007;Thom et al, 2011;Tai et al, 2016).…”

Section: Therapeuticsmentioning

confidence: 99%

GSK3β and Tau Protein in Alzheimer’s Disease and Epilepsy

Toral-Ríos

Pichardo-Rojas

Alonso-Vanegas

et al. 2020

Front. Cell. Neurosci.

111

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Alzheimer's disease (AD) is the most common form of dementia present in older adults; its etiology involves genetic and environmental factors. In recent years, epidemiological studies have shown a correlation between AD and chronic epilepsy since a considerable number of patients with AD may present seizures later on. Although the pathophysiology of seizures in AD is not completely understood, it could represent the result of several molecular mechanisms linked to amyloid beta-peptide (Aβ) accumulation and the hyperphosphorylation of tau protein, which may induce an imbalance in the release and recapture of excitatory and inhibitory neurotransmitters, structural alterations of the neuronal cytoskeleton, synaptic loss, and neuroinflammation. These changes could favor the recurrent development of hypersynchronous discharges and epileptogenesis, which, in a chronic state, favor the neurodegenerative process and influence the cognitive decline observed in AD. Supporting this correlation, histopathological studies in the brain tissue of temporal lobe epilepsy (TLE) patients have revealed the presence of Aβ deposits and the accumulation of tau protein in the neurofibrillary tangles (NFTs), accompanied by an increase of glycogen synthase kinase-3 beta (GSK3β) activity that may lead to an imminent alteration in posttranslational modifications of some microtubule-associated proteins (MAPs), mainly tau. The present review is focused on understanding the pathological aspects of GSK3β and tau in the development of TLE and AD.

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Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models

Cited by 54 publications

References 208 publications

Epilepsy in Neurodegenerative Dementias: A Clinical, Epidemiological, and EEG Study

Epilepsy in Neurodegenerative Dementias: A Clinical, Epidemiological, and EEG Study

Neurodegenerative pathways as targets for acquired epilepsy therapy development

GSK3β and Tau Protein in Alzheimer’s Disease and Epilepsy

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