The 1-42 Isoform of Amyloid Beta Reduces Cell Viability of Salmonella enterica
Dr. Gerald Griffin
Alzheimer's disease (AD) is the sixth-leading cause of death in the United States. In fact, one out of every eight Americans aged sixty-five and older will develop the disease. One pathological hallmark associated with AD and other forms of dementia is the over-accumulation of the peptide amyloid beta. While amyloid beta is present at low levels in all humans, its function is a source of great debate. The peptide has been shown to reduce the viability of microbes that have invaded the central nervous system. However, this finding has only been demonstrated once so far. The present work tested the hypothesis that amyloid beta exerts antimicrobial activity against Salmonella enterica (S. enterica), a leading cause of meningitis. After treating S. enterica with a range of concentrations (1pM-1microM) of both major isoforms of amyloid beta (1-40 and 1-42), we measured bacterial cell viability with the alamar blue assay. Our results revealed that the 1-42 isoform, but not the 1-40 isoform of amyloid beta, had an effect on bacterial growth. More specifically, administration of 10pM of amyloid beta (1-42 isoform) reduced cell viability over 20 percent (compared to vehicle control; F=32.91, p< 0.0001). This result extends the finding that amyloid beta has an anti-microbial function. Moreover, our results indicate that the 1-42 isoform, enriched in amyloid beta plaques associated with dementia, has unique properties that allow it to reduce the growth of S. enterica. Lastly, our data suggest that the peptide can exert antimicrobial effects at a concentration (10pM) lower than that associated with protein misfolding and the plaque formation associated dementia. While ongoing work is being performed to dissect the mechanisms underlying these findings, our data supports the hypothesis that amyloid beta release in vivo is prompted by microbial infection of the central nervous system.
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