Alzheimer Disease and Epilepsy: A Mendelian Randomization Study
Yi Fang1, Xiaoli Si1, Jiali Wang1
1From the Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Neurology
|May 24, 2023
Summary
This study found a causal link between Alzheimer disease (AD) and generalized epilepsy, and suggests AD may increase focal epilepsy risk. It also indicates a potential link between focal epilepsy and AD development.
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- Observational studies suggest a bidirectional relationship between Alzheimer disease (AD) and epilepsies, but causality remains debated.
- This study investigates the causal association between genetic predisposition to AD, AD cerebrospinal fluid (CSF) biomarkers, and various epilepsy types.
Approach:
- Utilized a 2-sample, bidirectional Mendelian randomization (MR) method with large-scale genome-wide association study data.
- Included genetic instruments for AD, CSF biomarkers (Aβ42, pTau), and detailed epilepsy phenotypes from European ancestry populations.
- Employed generalized summary data-based MR for main analyses and multiple sensitivity analyses for robustness.
Key Points:
- Genetic predisposition to AD was associated with increased risk of generalized epilepsy and focal epilepsy with hippocampal sclerosis (focal HS).
- Reverse analysis suggested a potential causal effect of focal HS on AD development.
- Genetically predicted lower CSF Aβ42 levels were linked to a higher risk of generalized epilepsy.
Conclusions:
- This MR study provides evidence supporting a causal relationship between Alzheimer disease, amyloid pathology, and generalized epilepsy.
- Findings indicate a close association between AD and focal HS, highlighting the need for seizure screening in AD patients.
- The study suggests exploring the role of seizures as a potential modifiable risk factor in Alzheimer disease.
