Tau Related Pathways as a Connecting Link between Epilepsy and Alzheimer's Disease

Yam Nath Paudel, Efthalia Angelopoulou, Nigel C. Jones, Terence J. O'brien, Patrick Kwan, Christina Piperi, Iekhsan Othman, Mohd Farooq Shaikh

Research output: Contribution to journalReview ArticleResearchpeer-review

26 Citations (Scopus)


Emerging findings point toward an important interconnection between epilepsy and Alzheimer's disease (AD) pathogenesis. Patients with epilepsy (PWE) commonly exhibit cognitive impairment similar to AD patients, who in turn are at a higher risk of developing epilepsy compared to age-matched controls. To date, no disease-modifying treatment strategy is available for either epilepsy or AD, reflecting an immediate need for exploring common molecular targets, which can delineate a possible mechanistic link between epilepsy and AD. This review attempts to disentangle the interconnectivity between epilepsy and AD pathogenesis via the crucial contribution of Tau protein. Tau protein is a microtubule-associated protein (MAP) that has been implicated in the pathophysiology of both epilepsy and AD. Hyperphosphorylation of Tau contributes to the different forms of human epilepsy and inhibition of the same exerted seizure inhibitions and altered disease progression in a range of animal models. Moreover, Tau-protein-mediated therapy has demonstrated promising outcomes in experimental models of AD. In this review, we discuss how Tau-related mechanisms might present a link between the cause of seizures in epilepsy and cognitive disruption in AD. Untangling this interconnection might be instrumental in designing novel therapies that can minimize epileptic seizures and cognitive deficits in patients with epilepsy and AD.

Original languageEnglish
Pages (from-to)4199-4212
Number of pages14
JournalACS Chemical Neuroscience
Issue number10
Publication statusPublished - 16 Oct 2019


  • Alzheimer's disease
  • cognitive decline
  • epilepsy
  • seizure
  • Tau protein

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