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Review
. 2018 Apr 5;19(4):1092.
doi: 10.3390/ijms19041092.

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

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Free PMC article
Review

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

Marina P Sánchez et al. Int J Mol Sci. .
Free PMC article

Abstract

Patients with dementia present epilepsy more frequently than the general population. Seizures are more common in patients with Alzheimer's disease (AD), dementia with Lewy bodies (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) than in other dementias. Missense mutations in the microtubule associated protein tau (MAPT) gene have been found to cause familial FTD and PSP, while the P301S mutation in MAPT has been associated with early-onset fast progressive dementia and the presence of seizures. Brains of patients with AD, LBD, FTD and PSP show hyperphosphorylated tau aggregates, amyloid-β plaques and neuropil threads. Increasing evidence suggests the existence of overlapping mechanisms related to the generation of network hyperexcitability and cognitive decline. Neuronal overexpression of tau with various mutations found in FTD with parkinsonism-linked to chromosome 17 (FTDP-17) in mice produces epileptic activity. On the other hand, the use of certain antiepileptic drugs in animal models with AD prevents cognitive impairment. Further efforts should be made to search for plausible common targets for both conditions. Moreover, attempts should also be made to evaluate the use of drugs targeting tau and amyloid-β as suitable pharmacological interventions in epileptic disorders. The diagnosis of dementia and epilepsy in early stages of those diseases may be helpful for the initiation of treatments that could prevent the generation of epileptic activity and cognitive deterioration.

Keywords: Alzheimer’s disease; FTDP-17 mouse model; cognitive impairment; dementia; epilepsy; mouse models; neuronal excitability; seizures; tau.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The expression of human TauVLW transgene in FTDP-17 mouse model causes many of the neurological and behavioral abnormalities found in patients with FTDP-17. (A) Examples of hyperphosphorylated tau aggregates in brain of FTDP-17 mice at 18 months of age. AT8 tau aggregates in neurons of (a) the CA3 and (c) the CA1 region of the hippocampus; PHF1 tau aggregates in (b) dentate gyrus and (d) amygdala (scale bar corresponds to 32 um in (a), 52 um in (b, c) and 28 um in (d)). (B) FTDP-17 mice show epileptic activity. (a) Intracranial record of background activity in control mice; (b) interictal activity, (b1) spike, (b2) polyspike, (b3,4) spike and wave and (b5) polyspike and wave complexes. (C) FTDP-17 mice have a higher sensitivity to the PTZ epileptogenic agent. The percentages of mice showing PTZ-induced myoclonic jerks (a and b) and generalized seizures (c and d) are higher in FTDP-17 mice than in controls. (D) Seizures induced by PTZ in FTDP-17 mice are more severe than those in control mice. The latency for PTZ-induced seizure onset is shorter (a) and the length of seizures is longer (b) in FTDP-17 mice compared to control mice. * p < 0.05; ** p < 0.01; *** p < 0.001 (n = 15–24).

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References

    1. Forsgren L., Edvinsson S.O., Blomquist H.K., Heijbel J., Sidenvall R. Epilepsy in a population of mentally retarded children and adults. Epilepsy Res. 1990;6:234–248. doi: 10.1016/0920-1211(90)90079-B. - DOI - PubMed
    1. Hesdorffer D.C., Hauser W.A., Annegers J.F., Kokmen E., Rocca W.A. Dementia and adult-onset unprovoked seizures. Neurology. 1996;46:727–730. doi: 10.1212/WNL.46.3.727. - DOI - PubMed
    1. Sherzai D., Losey T., Vega S., Sherzai A. Seizures and dementia in the elderly: Nationwide Inpatient Sample 1999–2008. Epilepsy Behav. 2014;36:53–56. doi: 10.1016/j.yebeh.2014.04.015. - DOI - PubMed
    1. Amatniek J.C., Hauser W.A., DelCastillo-Castaneda C., Jacobs D.M., Marder K., Bell K., Albert M., Brandt J., Stern Y. Incidence and predictors of seizures in patients with Alzheimer’s disease. Epilepsia. 2006;47:867–872. doi: 10.1111/j.1528-1167.2006.00554.x. - DOI - PubMed
    1. Mendez M.F., Catanzaro P., Doss R.C., ARguello R., Frey W.H. Seizures in Alzheimer’s disease: Clinicopathologic study. J. Geriatr. Psychiatry Neurol. 1994;7:230–233. doi: 10.1177/089198879400700407. - DOI - PubMed
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