Increased Incidence of Epilepsy in a Brain Bank Alzheimer's Disease Cohort and Its Association With TDP-43 Pathology

Evidence suggests Alzheimer's disease (AD) patients are at increased risk of epilepsy and that seizure incidence is associated with faster cognitive decline. Previous studies indicate hyperphosphorylated tau may play a role in this disease association; however, abnormal TDP-43 and α-synuclein deposition have not been extensively examined.

Clinical and neuropathological records of AD cases over a 5-year period were retrieved from the London Neurodegenerative Diseases Brain Bank. The 114 cases were categorised into three groups: AD plus epilepsy, AD plus hippocampal sclerosis (HS) and AD only. Semi-quantitative scores for tau, TDP-43 and α-synuclein pathology within the middle temporal gyrus, hippocampus and amygdala were compared between groups.

A 12% incidence of epilepsy and/or epileptic symptomology was found among the cohort. Twelve cases (11%) showed HS. No significant difference in tau pathology scores was seen between groups. However, a significantly higher score for TDP-43 was seen in AD plus epilepsy compared with AD only in the middle temporal gyrus (p = 0.004). The burden of α-synuclein pathology was increased in the amygdala of AD plus epilepsy and AD plus HS.

The incidence of epilepsy within this AD cohort is higher than expected within the general population (even when matched for age), and this may be associated with increased TDP-43 burden. Understanding the relationship between AD and epilepsy may highlight mechanisms of cellular damage and tissue vulnerability.