Lam AD, Thibault EG, Mayblyum DV, Hsieh S, Pellerin KR, Sternberg EJ, Viswanathan A, Buss S, Sarkis RA, Jacobs HI, Johnson KA, Sperling RA. Association of Seizure Foci and Location of Tau and Amyloid Deposition and Brain Atrophy in Patients With Alzheimer Disease and Seizures. Neurology. 2024 Nov 12;103(9):e209920. Epub 2024 Sep 27 PubMed. Correction.
Recommends
Please login to recommend the paper.
Comments
McGill University
The study from Lam et al. focuses on assessing the relationship between epileptiform activity found in Alzheimer’s disease (AD) patients and the pathophysiological changes characterizing the disease (i.e., Aβ, tau and cortical atrophy). They focus on a very unique and clinically well-characterized set of AD patients that present epileptiform activity and compare them to a group of AD patients without epileptiform activity. The authors suggest that higher tau deposition is observed in the hemisphere affected by epileptiform activity.
The idea that asymmetric distributions of AD pathology could be related to epileptiform activity is in fact very interesting. This aligns well with the notion that disrupted neuronal dynamics are related to the pathological processes underlying AD. If aberrant neural activity related to epilepsy is indeed linked to proteinopathy spreading or acceleration, it would be expected to observe asymmetric distribution of pathological depositions of Aβ and tau, which would be more pronounced in the affected hemisphere, as reported in the paper.
Another interesting point for discussion is that the authors suggest that tau pathology leads to hyperactivity, which has been supported by some previous finding as reviewed by Harris et al., 2020. Although the patient population used in this study is indeed very unique in its nature, it is however important to note that future studies with ideally larger samples and longitudinal designs are needed to better characterize the directionality of the reported associations. An alternative explanation to these findings could be that tau-independent hyperactivity (which may be related for example to the preceding impact of earlier Aβ deposition) is actually promoting tau accumulation/spreading in the affected hemisphere, which would be reflected as higher asymmetries in tau binding, as reported in the paper.
Overall, I think the paper supports the notion that epileptiform activity is related to increased proteinopathy deposition and provides room for exciting discussion. These findings echo what has been previously reported, strengthening the idea that aberrant neuronal activity represents a key player in the cascade of event underlying AD.
Make a Comment
To make a comment you must login or register.