Alzheimer’s disease (AD), the most prevalent age-related neurodegenerative disorder, is characterized pathologically by the accumulation of β-amyloid (Aβ) plaques and tau-laden neurofibrillary tangles. Interestingly, up to 50% of AD cases exhibit a third prevalent neuropathology: the aggregation of α-synuclein into Lewy bodies. Importantly, the presence of Lewy body pathology in AD is associated with a more aggressive disease course and accelerated cognitive dysfunction. Thus, Aβ, tau, and α-synuclein may interact synergistically to promote the accumulation of each other. In this study, we used a genetic approach to generate a model that exhibits the combined pathologies of AD and dementia with Lewy bodies (DLB). To achieve this goal, we introduced a mutant human α-synuclein transgene into 3xTg-AD mice. As occurs in human disease, transgenic mice that develop both DLB and AD pathologies (DLB-AD mice) exhibit accelerated cognitive decline associated with a dramatic enhancement of Aβ, tau, and α-synuclein pathologies. Our findings also provide additional evidence that the accumulation of α-synuclein alone can significantly disrupt cognition. Together, our data support the notion that Aβ, tau, and α-synuclein interact in vivo to promote the aggregation and accumulation of each other and accelerate cognitive dysfunction.

We sought to determine if sex impacts the cognitive and neuropathological phenotype of the 3xTg-AD mice. We find that male and female 3xTg-AD mice show comparable impairments on Morris water maze (MWM) and inhibitory avoidance (IA) at 4 months. Shortly thereafter, however, the cognitive performance varies among the sexes, with females performing worse than males. These behavioral differences are not attributable to differences in Aβ or tau levels. The behavioral effect is transient as from 12 months onward, the disparity is no longer apparent. Because females perform worse than males on stressful tasks, we explored their corticosterone responses, and find that young female 3xTg-AD mice show markedly heightened corticosterone response after 5 days of MWM training compared to age-matched male 3xTg-AD mice; this difference is no longer apparent in older mice. Thus, the enhanced corticosterone response of the young female mice likely underlies their poorer performance on stressful tasks.

In glycogen storage disease type III (GSD III), liver aminotransferases tend to normalize with age giving an impression that hepatic manifestations improve with age. However, despite dietary treatment, long-term liver complications emerge. We present a GSD III liver natural history study in children to better understand changes in hepatic parameters with age. Methods: We reviewed clinical, biochemical, histological, and radiological data in pediatric patients with GSD III, and performed a literature review of GSD III hepatic findings. Results: Twenty-six patients (median age 12.5 years, range 2-22) with GSD IIIa (n = 23) and IIIb (n = 3) were enrolled in the study. Six of seven pediatric patients showed severe fibrosis on liver biopsy (median [range] age: 1.25 [0.75-7] years). Markers of liver injury (aminotransferases), dysfunction (cholesterol, triglycerides), and glycogen storage (glucose tetrasaccharide, Glc 4) were elevated at an early age, and decreased significantly thereafter (p < 0.001). Creatine phosphokinase was also elevated with no significant correlation with age (p = 0.4). Conclusion: Liver fibrosis can occur at an early age, and may explain the decrease in aminotransferases and Glc 4 with age. Our data outlines the need for systematic follow-up and specific biochemical and radiological tools to monitor the silent course of the liver disease process.

The delayed reporting of antimicrobial susceptibility testing remains a limiting factor in clinical decision-making in the treatment of bacterial infection. This study evaluates the use of forward laser light scatter (FLLS) to measure bacterial growth for the early determination of antimicrobial susceptibility. Three isolates each (two clinical isolates and one reference strain) of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were tested in triplicate using two commercial antimicrobial testing systems, the Vitek2 and the MicroScan MIC panel, to challenge the BacterioScan FLLS. The BacterioScan FLLS showed a high degree of categorical concordance with the commercial methods. Pairwise comparison with each commercial system serving as a reference standard showed 88.9% agreement with MicroScan (two minor errors) and 72.2% agreement with Vitek (five minor errors). FLLS using the BacterioScan system shows promise as a novel method for the rapid and accurate determination of antimicrobial susceptibility.