Proposing a minimal set of metrics and methods to predict probabilities of amyloidosis disease and onset age in individuals.

ABSTRACT: Many amyloid-driven pathologies have both genetic and stochastic components where assessing risk of disease development requires a multifactorial assessment where many of the variables are poorly understood. Risk of transthyretin-mediated amyloidosis is enhanced by age and mutation of the transthyretin (TTR) gene, but amyloidosis is not directly initiated by mutated TTR proteins. Nearly all of the 150+ known mutations increase dissociation of the homotetrameric protein structure and increase the probability of an individual developing a TTR amyloid disease late in life. TTR amyloidosis is caused by dissociated monomers that are destabilized and refold into an amyloidogenic form. Therefore, monomer concentration, monomer proteolysis rate, and structural stability are key variables that may

SUBMITTER: Criddle RS 

PROVIDER: S-EPMC7746394 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature