Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder without a cure, despite the enormous number of investigations and therapeutic approaches. AD is a consequence of microglial responses to “damage signals”, such as aggregated tau oligomers, which trigger a neuro-inflammatory reaction, promoting the misfolding of cytoskeleton structure. Since AD is the most prevalent cause of dementia in the elderly (>60 years old), new treatments are essential to improve the well-being of affected subjects. The pharmaceutical industry has not developed new drugs with efficacy for controlling AD. In this context, major attention has been given to nutraceuticals and novel bioactive compounds, such as molecules from the Andean Shilajit (AnSh), obtained from the Andes of Chile. Primary cultures of rat hippocampal neurons and mouse neuroblastoma cells were evaluated to examine the functional and neuroprotective role of different AnSh fractions. Our findings show that AnSh fractions increase the number and length of neuronal processes at a differential dose. All fractions were viable in neurons. The AnSh fractions inhibit tau self-aggregation after 10 days of treatment. Finally, we identified two candidate molecules in M3 fractions assayed by UPLC/MS. Our research points to a novel AnSh-derived fraction that is helpful in AD. Intensive work toward elucidation of the molecular mechanisms is being carried out. AnSh is an alternative for AD treatment or as a coadjuvant for an effective treatment.
Background Enlarged Perivascular Spaces (EPVS) are associated with small vessel disease. The objective of this study was to develop semi‐automated techniques for the quantification of EPVS burden. Method An intensity‐based threshold was used to identify EPVS. A threshold of maximum plus two standard deviations of intensities of normal‐appearing white matter in the supratentorial region was used to identify EPVS. To compare the performance of the semi‐automatic approach for EPVS segmentation to visually rated EPVS scores, two regions of interest were outlined in the basal ganglia (BG) region and the centrum semiovale (CS). For both these regions, a score was generated by an experienced neurologist by visually counting the number of EPVS with a score of zero representing the absence of any EPVS, a score of 1 representing 1‐10 EPVS, a score of 2 representing 11‐20 EPVS, a score of 3 representing 21‐40 EPVS, and a score of 4 representing >40 EPVS. The semi‐automatic approach provided a count of the number of EPVS that were converted to grade using the same scaling as the visual approach. Spearman Rank Order Correlation Coefficient was calculated to estimate the correlation between the two methods. Mann‐Whitney U tests of ranks are employed to determine if any group differences are present. Finally, Cohen’s kappa was used to compare the concordance between measures between the two different methods. Result Figure 2 shows the results of the segmentation in subjects with differing EPVS burden. Spearman Rank Order Correlation analysis showed a significant correlation between the EPVS scores determined visually and those obtained semi‐automatically in 60 subjects (Table 1). Results of the Mann‐Whitney U tests showed that there was no statistically significant (p > 0.05) difference between the EPVS scores obtained visually and using the semi‐automatic approach (Table 2). Cohen's κ test showed that there was moderate agreement between the two estimation methods in the BG (κ = .522, p < .0001) and CS regions (κ = .571, p < .0001). Conclusion The developed method showed good concordance with expert visual read and can provide quantitative measures of EPVS burden (counts and volume) for evaluation of vascular risk.
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