Department of Psychological Sciences, Purdue University, West Lafayette, Indiana, USA.
Department of Biological Sciences, Southern Methodist University, Dallas, Texas, USA.
Epilepsia Open. 2023 Jun;8(2):609-622. doi: 10.1002/epi4.12744. Epub 2023 Apr 24.
Epilepsy can be comorbid with cognitive impairments. Recent evidence suggests the possibility that cognitive decline in epilepsy may be associated with mechanisms typical of Alzheimer's disease (AD). Neuropathological hallmarks of AD have been found in brain biopsies surgically resected from patients with drug-resistant epilepsies. These include hyperphosphorylation of the tau protein (p-tau) that aggregates into neuropil threads (NT) or neurofibrillary tangles (NFT), as well as the presence of β-amyloid (Aβ) deposits. While recent studies agree on these AD neuropathological findings in epilepsy, some contrast in their correlation to cognitive decline. Thus, to further address this question we determined the abundance of p-tau and Aβ proteins along with their association with cognitive function in 12 cases of refractory epilepsy.
Cortical biopsies surgically extracted from the temporal lobes of patients with refractory epilepsy were processed for immunohistology and enzyme-linked immunoassays to assess distribution and levels, respectively, of p-tau (Antibodies: Ser202/Thr205; Thr205; Thr181) and Aβ proteins. In parallel, we measured the activation of mechanistic target of rapamycin (mTOR) via p-S6 (Antibodies: Ser240/244; Ser235/236). Pearson correlation coefficient analysis determined associations between these proteins and neurophysiological scores for full-scale intelligence quotient (FSIQ).
We found a robust presence of p-tau (Ser202/Thr205)-related NT and NFT pathology, as well as Aβ deposits, and p-S6 (Ser240/244; Ser235/236) in the epilepsy biopsies. We found no significant correlations between p-tau (Thr205; Thr181), Aβ, or mTOR markers with FSIQ scores, although some correlation coefficients were modest to strong.
These findings strongly support the existence of hyperphosphorylated tau protein and Aβ deposits in patients with human refractory epilepsy. However, their relation to cognitive decline is still unclear and requires further investigation.
癫痫可并发认知障碍。最近的证据表明，癫痫认知能力下降可能与阿尔茨海默病（AD）的典型机制有关。在药物难治性癫痫患者手术切除的脑活检中发现了 AD 的神经病理学特征。这些特征包括微管相关蛋白 tau（p-tau）的过度磷酸化，其聚集成神经原纤维缠结（NFT）或神经纤维缠结（NT），以及β-淀粉样蛋白（Aβ）的沉积。虽然最近的研究都同意癫痫中的这些 AD 神经病理学发现，但它们与认知能力下降的相关性存在一些差异。因此，为了进一步解决这个问题，我们在 12 例耐药性癫痫患者中确定了 p-tau 和 Aβ 蛋白的丰度及其与认知功能的相关性。
对药物难治性癫痫患者颞叶手术切除的皮质活检进行免疫组织化学和酶联免疫吸附测定，分别评估 p-tau（抗体：Ser202/Thr205；Thr205；Thr181）和 Aβ 蛋白的分布和水平。同时，我们通过 p-S6（抗体：Ser240/244；Ser235/236）测量了雷帕霉素靶蛋白（mTOR）的激活。Pearson 相关系数分析确定了这些蛋白与全智商（FSIQ）神经生理评分之间的关联。
我们在癫痫活检中发现了大量的 p-tau（Ser202/Thr205）相关的 NT 和 NFT 病理学，以及 Aβ 沉积和 p-S6（Ser240/244；Ser235/236）。我们没有发现 p-tau（Thr205；Thr181）、Aβ 或 mTOR 标志物与 FSIQ 评分之间有显著相关性，尽管有些相关系数从弱到中等。
这些发现强烈支持人类耐药性癫痫患者存在过度磷酸化的 tau 蛋白和 Aβ 沉积。然而，它们与认知能力下降的关系仍不清楚，需要进一步研究。
