Background: Dysfunction of γ-aminobutyric acid (GABA) (B) receptors has been implicated in the pathogenesis of temporal lobe epilepsy (TLE). Objective: To evaluate the genetic contribution of cloned human GABA(B) receptors to TLE. Methods: The authors genotyped 141 patients (78 women and 63 men; mean age = 49.1 ± 18.0 years) with nonlesional TLE and 372 age- and sex-matched normal individuals for the known polymorphism G1465A in the human GABA(B) receptor 1 [GABA(B[1])] gene. Results: There was a highly significant overrepresentation of the G1465A heterozygote in patients with TLE compared with controls. The A/G genotype was found in 17% of the 141 patients with TLE and in only 0.5% of the 372 controls (p < 0.0001). The authors also found that patients carrying the A allele had a significantly higher risk (p = 0.003, OR = 6.47, 95% CI = 2.02 to 20.76) of developing drug-resistant TLE. Furthermore, the age at onset of seizures tended to be lower in patients with A/G genotype, but the difference was not significant. Conclusions: The results of this study indicate that the GABA(B[1]) polymorphism (G1465A) confers a highly increased susceptibility to TLE. Moreover, it seems to influence the severity of this common epileptic disorder.

Alzheimer’s disease (AD), a neurodegenerative disease, is linked to a variety of internal and external factors present from the early stages of the disease. There are several risk factors related to the pathogenesis of AD, among these exosomes and microRNAs (miRNAs) are of particular importance. Exosomes are nanocarriers released from many different cell types, including neuronal cells. Through the transfer of bioactive molecules, they play an important role both in the maintenance of physiological and in pathological conditions. Exosomes could be carriers of potential biomarkers useful for the assessment of disease progression and for therapeutic applications. miRNAs are small noncoding endogenous RNA sequences active in the regulation of protein expression, and alteration of miRNA expression can result in a dysregulation of key genes and pathways that contribute to disease development. Indeed, the involvement of exosomal miRNAs has been highlighted in various neurodegenerative diseases, and this opens the possibility that dysregulated exosomal miRNA profiles may influence AD disease. The advances in exosome-related biomarker detection in AD are summarized. Finally, in this review, we highlight the use of exosomal miRNAs as essential biomarkers in preclinical and clinical studies in Alzheimer’s disease, also taking a look at their potential clinical value.

Summary:  Purpose: To clarify the possible role of other factors including the ApoE ɛ4 allele for memory decline in temporal lobe epilepsy (TLE). Methods: We conducted a neuropsychological and molecular study in 138 consecutive patients (78 female patients; mean age, 50.2 years, SD ± 17.9; range, 14 to 87 years) with mild nonlesional TLE, who rarely or never had seizures at long‐term follow‐up. The mean age at seizure onset was 33.0 years (SD, ±21.7), and the mean duration of epilepsy was 17.1 years (SD, ±15.7). Results: Thirty‐four (25%) of 138 patients had test scores indicating verbal learning deficit (VLD). The presence of an ApoE ɛ4 allele was associated with an increased risk of VLD (OR, 4.18; 95% CI, 1.66–10.55). The effect of the ApoE genotype was independent of both the age at epilepsy onset and disease duration as well as of a low educational level, which were separately associated with VLD (p values = 0.045, 0.001, and 0.001, respectively). A significant linear trend (p = 0.005) was seen in the relation between disease duration and cognitive impairment, with the highest risk being in patients with an epilepsy duration ≥25.5 years (OR, 7.06; 95% CI, 1.67–29.85), especially if they carried the ɛ4 allele (OR, 32.29; 95% CI, 5.23–195.72). Conclusions: These results provide evidence for an alteration in cognitive performance as a function of the presence of the ApoE ɛ4 allele and point to the critical role of disease duration itself for cognitive impairment in TLE.