Association between APOE polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis S. N. Yeni a ,C ¸.O ¨ zkara a , N. Buyru b , O. Baykara b , L. Hanog ˘ lu c , N. Karaag ˘ ac a , E. O ¨ zyurt d and M. Uzan d a Department of Neurology; b Department of Medical Biology, c Bakırko ¨y Neurology Centre, Laboratory of Neuropsychology; and d Department of Neurosurgery, Cerrahpas ¸ a Medical School, I _ stanbul University, Cerrahpas ¸ a, I _ stanbul, Turkey Keywords: apolipoprotein E, genetics, hippocampal sclerosis, mesial temporal lobe epilepsy, risk factor Received 9 February 2004 Accepted 7 August 2004 To evaluate the hypothetical link between apolipoprotein E (APOE) polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and whether presence of APOE epsilon4 allele shortens the latent period between febrile seizures and epilepsy. A further interest is whether presence of APOE epsilon4 allele has an impact on severity of the disease. Forty-seven patients with MTLE-HS were compared with 62 controls. APOE polymorphisms were determined from lymphocytes by standard methods. Eight patients (17%) and 10 controls (16.1%) were demon- strated to have one APOE epsilon4 allele. There was not any statistically significant difference in APOE epsilon4 frequency between patients and controls (P > 0.05). There was not any difference statistically according to onset age of epilepsy and the presence of APOE epsilon4 allele within patient group. APOE epsilon4 polymor- phisms did not influence the severity of epilepsy. APOE epsilon4 polymorphisms had no impact on outcome after surgery. Patients with bilateral memory deficits, bilateral hippocampal atrophy and with bilateral epileptiform interictal EEG transients, were independently compared with patients having unilateral features and there were not any statistically significant differences. This study has found no association between APOE epsilon4 polymorphisms and presentation of MTLE-HS in a group of Turkish patients. Introduction Apolipoprotein is a multifunctional compound with an expanding role in the understanding of neurodegener- ative diseases such as Alzheimer disease (AD). There is consensus over the inheritance of apolipoprotein E (APOE) epsilon4 allele as a risk factor for AD and it has been associated with an earlier age of onset (Poirier, 2002). In animal studies, it was shown that in presence of APOE epsilon4 allele, brain’s ability to repair damage and form new synapses is impaired (Poirier, 1994). It has also been proposed that APOE epsilon4 has a role in regulation of lipid homeostasis in the central nervous system (CNS) and coordination of cholesterol transport during reinnervation of the injured CNS (Poirier, 2002). With increasing evidence of the role of APOE in repair mechanisms in the brain, APOE polymorphisms and their link to temporal lobe epilepsy has attracted attention. As, APOE epsilon4 allele promotes depos- ition of b amyloid (Ab) in brain tissue (Poirier, 2002), studies on expression and presence of Ab precursor protein (b APP) and Ab have been performed and were demonstrated in temporal lobe specimens yielding a link between APOE epsilon4 allele and TLE (Mac- kenzie and Miller, 1994; Sheng et al., 1994; Gouras et al., 1997). However, some further studies were not able to find a link between TLE and APOE polymor- phisms (Blu¨mcke et al., 1997; Gamberdella et al., 1999). There are published data showing a high prevalence of epilepsy and febrile seizures (FS) in families of pa- tients with MTLE-HS (Abou-Khalil et al., 1993). Qualitative analysis of MRI have also showed abnor- malities suggestive of MTS in 57% of individuals with variable clinical expression in MTLE families (Ko- bayashi et al., 2001). These observations strongly indi- cate that MTS has a genetic background which may act as a risk factor to increase susceptibility to epilepsy. However, prevalence of acquired risk factors such as complicated FS, CNS infections are high amongst pa- tients with MTLE-HS pointing out the acquired nature of the disease. Thus, APOE polymorphisms have attracted attention because of its role in repair mecha- nisms after injury. Based on pathological data derived from temporal lobe specimens of TLE patients, APOE may well be accepted one of the susceptibility genes. Correspondence: S. Naz Yeni, _ Istanbul University Cerrahpas¸ a Med- ical School Department of Neurology, Cerrahpas¸ a _ Istanbul-Turkey 34303 (tel.: 90 212 414 30 00-21078; fax: 90 212 632 96 96; e-mail: snaz@atlas.net.tr). Ó 2005 EFNS 103 European Journal of Neurology 2005, 12: 103–107