Epigenetic mechanisms play an important role in the development and progression of various neurodegenerative diseases. Abnormal methylation of numerous genes responsible for regulation of transcription, DNA replication, and apoptosis has been linked to Alzheimer’s disease (AD) pathology. We have recently performed whole transcriptome profiling of familial early‐onset Alzheimer’s disease (fEOAD) patient‐derived fibroblasts. On this basis, we demonstrated a strong dysregulation of cell cycle checkpoints and DNA damage response (DDR) in both fibroblasts and reprogrammed neurons. Here, we show that the aging‐correlated hypermethylation of KLF14 and TRIM59 genes associates with abnormalities in DNA repair and cell cycle control in fEOAD. Based on the resulting transcriptome networks, we found that the hypermethylation of KLF14 might be associated with epigenetic regulation of the chromatin organization and mRNA processing followed by hypermethylation of TRIM59 likely associated with the G2/M cell cycle phase and p53 role in DNA repair with BRCA1 protein as the key player. We propose that the hypermethylation of KLF14 could constitute a superior epigenetic mechanism for TRIM59 hypermethylation. The methylation status of both genes affects genome stability and might contribute to proapoptotic signaling in AD. Since this study combines data obtained from various tissues from AD patients, it reinforces the view that the genetic methylation status in the blood may be a valuable predictor of molecular processes occurring in affected tissues. Further research is necessary to define a detailed role of TRIM59 and KLF4 in neurodegeneration of neurons.

Background and Study Aim. Stimulation of the sympathetic nervous system and the hypothalamic‐pituitary‐adrenal axis are a crucial mechanism of adaptation to physical exercise, in particular in combat sports. This study assesses changes of the relevant hormonal profiles upon performance in selected combat sports. Material and Methods. Participants (130 men practicing combat sports at a high level) were divided by discipline: karate (K), taekwondo (T), and judo, wrestling, and sumo combined (JWS). Blood concentration of adrenaline, noradrenaline, cortisol, testosterone, and brain‐derived neurotrophic factor (BDNF) was determined before and after fighting. Results. Following fighting, the adrenaline concentration was significantly higher in all athletes, most markedly in K (p < 0.001). Baseline cortisol and BDNF levels did not differ among the groups and rose significantly in all the groups after the performance. Baseline testosterone concentration was slightly higher in K than in JSW and rose in all the groups to reach similar levels; the increase in T was significantly higher than in K. Conclusions. Despite substantial differences in the characteristics of the combat sports investigated, including the type of physical effort and the required balance between restraint and aggression, the performance in each of them gives rise to similar hormonal changes with a possible exception of karate showing higher stress hormone levels.

The overlap between progressive supranuclear palsy (PSP) and progressive non-fluent aphasia (PNFA) is being increasingly recognized. In this paper descriptive writing in patients with Richardson syndrome of progressive supranuclear palsy (PSP-RS) is compared to writing samples from patients with PNFA. Twenty-seven patients participated in the study: 17 with the clinical diagnosis of PSP-RS and 10 with PNFA. Untimed written picture description was administered during neuropsychological assessment and subsequently scored by two raters blinded to the clinical diagnosis. Lexical and syntactic content, as well as writing errors (e.g. omission and perseverative errors) were analyzed. In patients with PSP-RS both letter and diacritic mark omission errors were very frequent. Micrographia was present in 8 cases (47%) in PSP-RS group and in one case (10%) with PNFA. Perseverative errors did not differentiate between the groups. As omission errors predominate in writing of patients with PSP-RS, writing seems to be compromised mainly because of oculomotor deficits, that may alter visual feedback while writing.

Background: The rapid worldwide increase in the incidence of Alzheimer’s disease is associated with changing nutrition patterns. Recently, some articles have highlighted the link between Alzheimer’s disease and dietary cholesterol. It was found that elevated levels of some of its fractions in the brain and circulation affect metabolism. Summary: Previous studies have considered the relationship between Alzheimer’s disease and oxidized cholesterol molecules in the brain. To date, there are limited data available on the relationship between oxidized cholesterol in the brain and Alzheimer’s disease. There is a link between a diet high in cholesterol and its oxidized forms, leading to hypercholesterolemia, which is one of significant risk factors of dementia, and Alzheimer’s disease. Oxidized cholesterol can be absorbed in the small intestine and cross the blood-brain barrier, leading to increased inflammation and endogenous oxidative process. Animal-origin foods are sources of oxidized cholesterol, with cholesterol oxidation beginning already after slaughter and occurring during storage and processing. Key Messages: High-heat food preparation and storage of cooked products in the refrigerator followed by subsequent heating may significantly increase the amount of oxidized cholesterol products. Therefore, a diet low in cholesterol oxidation products and high in plants with antioxidative properties seems to be most preventable and should be implemented as early as possible.

The early diagnosis of Alzheimer’s disease