Juliana C Silva1, Lucy Vivash1, Charles B Malpas1,2, Yong Hao3, Catriona McLean4, Zhibin Chen1,5, Terence J O'Brien1,2, Nigel C Jones1, Patrick Kwan1,2. 1. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia. 2. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia. 3. Department of Neurology, Renji Hospital, Medical School, Shanghai Jiaotong University, Shanghai, China. 4. Department of Anatomical Pathology, Alfred Health, Melbourne, Victoria, Australia. 5. School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Abstract
OBJECTIVE: Cognitive impairment is common in patients with chronic drug-resistant temporal lobe epilepsy (TLE). Hyperphosphorylated tau (pTau) and amyloid-β (Aβ) plaques, pathological hallmarks of Alzheimer disease, have been hypothesized to play a mechanistic role. We investigated Aβ plaques and pTau prevalence in TLE patients who underwent resective surgery and correlated their presence with preoperative psychometric test scores and clinical factors. METHODS: Patients were retrospectively selected from the epilepsy surgery register of the Royal Melbourne Hospital, Australia. Sections from the resected temporal lobe were immunostained for pTau and Aβ plaques (antibodies: AT8, 1E8). The presence and severity of pathology were correlated with clinical characteristics, and verbal and visual learning functions as measured by the Verbal Pair Associates (VPA) test and Rey Complex Figure Test. RESULTS: Fifty-six patients (55% female) aged 20-68 years (median = 34 years) at surgery were included. Aβ plaques were detected in four patients (7%), all at the moderate level. There was no difference in duration, age at onset of epilepsy, or side of resection between patients with and without Aβ plaques. Sparse pTau was found in two patients (3.5%). Both had moderate Aβ plaques and were >50 years of age. Patients with Aβ plaques had a lower median score for the VPA hard assessment compared to those without (0 vs. 4; p = .02). There was otherwise no correlation between pathology and psychometric test scores. SIGNIFICANCE: Aβ plaques and pTau were uncommon in the resected brain tissue of patients who have undergone temporal lobectomy, and did not correlate with clinical characteristics or preoperative psychometric test scores, except for a lower VPA median score in patients with Aβ plaques. Therefore, considering the low prevalence of Aβ plaques and pTau herein observed, it is unlikely that cognitive impairment in TLE is driven by the same mechanisms as in Alzheimer disease.
OBJECTIVE: Cognitive impairment is common in patients with chronic drug-resistant temporal lobe epilepsy (TLE). Hyperphosphorylated tau (pTau) and amyloid-β (Aβ) plaques, pathological hallmarks of Alzheimer disease, have been hypothesized to play a mechanistic role. We investigated Aβ plaques and pTau prevalence in TLE patients who underwent resective surgery and correlated their presence with preoperative psychometric test scores and clinical factors. METHODS: Patients were retrospectively selected from the epilepsy surgery register of the Royal Melbourne Hospital, Australia. Sections from the resected temporal lobe were immunostained for pTau and Aβ plaques (antibodies: AT8, 1E8). The presence and severity of pathology were correlated with clinical characteristics, and verbal and visual learning functions as measured by the Verbal Pair Associates (VPA) test and Rey Complex Figure Test. RESULTS: Fifty-six patients (55% female) aged 20-68 years (median = 34 years) at surgery were included. Aβ plaques were detected in four patients (7%), all at the moderate level. There was no difference in duration, age at onset of epilepsy, or side of resection between patients with and without Aβ plaques. Sparse pTau was found in two patients (3.5%). Both had moderate Aβ plaques and were >50 years of age. Patients with Aβ plaques had a lower median score for the VPA hard assessment compared to those without (0 vs. 4; p = .02). There was otherwise no correlation between pathology and psychometric test scores. SIGNIFICANCE: Aβ plaques and pTau were uncommon in the resected brain tissue of patients who have undergone temporal lobectomy, and did not correlate with clinical characteristics or preoperative psychometric test scores, except for a lower VPA median score in patients with Aβ plaques. Therefore, considering the low prevalence of Aβ plaques and pTau herein observed, it is unlikely that cognitive impairment in TLE is driven by the same mechanisms as in Alzheimer disease.