Alzheimer's disease (AD) is characterized by a heterogeneous clinical course, and magnetic resonance imaging (MRI)-based phenotyping has increasingly been utilized to elucidate this variability. The l Show more
Alzheimer's disease (AD) is characterized by a heterogeneous clinical course, and magnetic resonance imaging (MRI)-based phenotyping has increasingly been utilized to elucidate this variability. The literature recognizes four predominant MRI phenotypes: typical, hippocampal-sparing, limbic-predominant, and minimal-atrophy. However, the compatibility of various MRI phenotyping methods remains insufficiently defined. This study aimed to assess the concordance between MRI phenotyping methods within a Serbian cohort consisting of 40 subjects. Four MRI phenotyping approaches were employed: scale-based, adjusted scale-based, volume-based, and thickness-based. The scale-based method exhibited moderate agreement with the adjusted scale-based approach and high concordance with volumetric methods. In contrast, the relationship between scale- and thickness-based phenotyping was less clear. The lack of significant agreement with demographic variables, along with the observed differences across clinical dementia rating (CDR) domains, further underscored the clinical heterogeneity among phenotypes. Overall, these findings suggest that visual scale-based MRI phenotyping may serve as a practical approach in resource-limited clinical settings where advanced methods are unavailable. However, the results must be interpreted with caution and require validation in larger independent cohorts. Further research is necessary to clarify the relationship between scale- and thickness-based phenotyping across different disease stages and to investigate discrepancies in demographic, apolipoprotein E (APOE)-related, and clinical phenotype patterns in this Serbian sample compared to other populations. Show less
Women with polycystic ovary syndrome (PCOS) has high incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). The development of PCOS-associated MASLD is accelerated by prepubert Show more
Women with polycystic ovary syndrome (PCOS) has high incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). The development of PCOS-associated MASLD is accelerated by prepubertal obesity, therefore, we analyzed the impact of postnatal overfeeding-induced obesity on the gut microbiota and hepatic lipid metabolism in the PCOS rat model. Wistar rats were divided into 4 groups, where treatment with 5α-dihydrotestosterone (5α-DHT) stimulated hyperandrogenemia (DHT groups), whereas litter size reduction induced early postnatal overfeeding and obesity (SL groups). The fecal microbiota composition and diversity was analyzed by 16S rRNA sequencing. The bacterial metabolites level was measured by mass spectrometry. Hematoxylin-eosin staining, Western blots, and qRT-PCR were used to analyze hepatic lipid metabolism. Our results show that postnatal overfeeding shifted the microbiota composition towards obesity-associated genera, while hyperandrogenemia led to reduced β-diversity and increased abundance of androgen-regulated genera. Interaction of treatments reduced α- and β-diversity and decreased the abundance of beneficial butyrate-producing genera Roseburia, Oscillospira, and Ruminococcus and butyric acid plasma level. Shift in microbiota composition and activity was accompanied by decreased expression of G-protein coupled receptor (GPR) 43, fasting-induced adipocyte factor (FIAF) and increased expression of lipoprotein lipase (LPL). In accordance with altered GPR43 and FIAF/LPL pathway, increased expression of lipogenic transcription factors was observed in SL-DHT animals, but this did not result in hepatic lipid deposition. Our results demonstrated that postnatal overfeeding contributes to decreased richness and changes in gut microbiota composition in the PCOS animal model that is associated with impaired hepatic lipid metabolism, which may accelerate development of MASLD. Show less