Comparison of amyloid-β, total tau and phospho-tau in clinical AD patients with and without epileptiform EEG patterns

Epilepsy is a relevant comorbidity of dementia due to Alzheimer's Disease (AD) and probably directly related to its pathology. We aimed to generate hypotheses how interictal epileptiform discharges (IEDs) may be associated with pathological levels of AD markers from cerebrospinal fluid (CSF).

To perform bivariate analyses between IEDs or EEG background slowing to CSF AD markers including amyloid-β42 to amyloid-β40 ratio (Aβ ratio), total tau and phospho-tau.

In this retrospective cross-sectional study, we identified 26 clinical AD patients who presented with at least one of three pathological neurodegeneration markers in the CSF (Aβ ratio ≤0.5, total tau ≥370 pg/ml, phospho-tau ≥66 pg/ml) and received at least one routine EEG.

IEDs and EEG background slowing were present in 5/26 and 14/26 patients, respectively. We observed that patients with IEDs or EEG background slowing had significantly lower phospho-tau levels than patients without (Cohen's d=0.91, P = 0.044 and Cohen's d=1.33, P = 0.005, respectively). Consistent with this, a positive history of seizures tended to be associated with lower phospho-tau levels (Cohen's d=0.79, P = 0.059). Moreover, phospho-tau levels were significantly correlated to dominant posterior EEG frequencies (Spearman's ρ=0.524, P = 0.006), and Aβ ratios were significantly lower in patients with normal EEG background frequencies than in those with EEG slowing (Cohen's d=1.31, P = 0.017).

Our bivariate analyses revealed the unexpected observation that the presence of IEDs was associated with lower rather than higher phospho-tau levels in clinical AD patients. This finding awaits further confirmation in a larger cohort.