Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease caused by a 10-nucleotide duplication-insertion in the BRI2 gene. FDD is clinically characterized by loss of vision, hearing impairment, cerebellar ataxia and dementia. The main neuropathologic findings in FDD are the deposition of Danish amyloid (ADan) and the presence of neurofibrillary tangles (NFTs). Here we investigated tau accumulation and truncation in double transgenic (Tg-FDD-Tau) mice generated by crossing transgenic mice expressing human Danish mutant BRI2 (Tg-FDD) with mice expressing human 4-repeat mutant Tau-P301S (Tg-Tau). Compared to Tg-Tau mice, we observed a significant enhancement of tau deposition in Tg-FDD-Tau mice. In addition, a significant increase in tau cleaved at aspartic acid (Asp) 421 was observed in Tg-FDD-Tau mice. Tg-FDD-Tau mice also showed a significant decrease in synaptophysin levels, occurring before widespread deposition of fibrillar ADan and tau can be observed. Thus, the presence of soluble ADan/mutant BRI2 can lead to significant changes in tau metabolism and synaptic dysfunction. Our data provide new in vivo insights into the pathogenesis of FDD and the pathogenic pathway(s) by which amyloidogenic peptides, regardless of their primary amino acid sequence, can cause neurodegeneration.
Natural antimicrobials can be added to help extend the shelf life of milk and reduce contamination potential, especially in developing countries. The levels of lactoferrin found in raw milk have not been thoroughly studied in regard to specific antibacterial activity against key pathogens. This study aimed to investigate various concentrations of lactoferrin as a biopreservative measure against Salmonella enterica and Escherichia coli O157:H7. Our results indicate that lactoferrin has potential as a biopreservative. These results will assist in the reduction of milk-borne illnesses in developing countries that may lack means for proper refrigeration.
Highlights• In the absence of proper refrigeration of raw milk, bacterial pathogens such as Salmonella and E. coli O157:H7 may cause illness. • Growth of each pathogen in raw milk was measured using a novel tetrazolium salt reduction assay.• Growth of Salmonella and E. coli O157:H7 was inhibited by lactoferrin in raw bovine milk.• Lactoferrin represents a safe means of milk preservation in developing countries lacking proper refrigeration.
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