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Autocatalytic fibril nucleation has recently been proposed to be adetermining factor for the spread of neurodegenerative diseases, but the sameprocess could also be exploited to amplify minute quantities of proteinaggregates in a diagnostic context. Recent advances in microfluidic technologyallow analysis of protein aggregation in micron-scale samples potentiallyenabling such diagnostic approaches, but the theoretical foundations for theanalysis and interpretation of such data are so far lacking. Here we studycomputationally the onset of protein aggregation in small volumes and show thatthe process is ruled by intrinsic fluctuations whose volume dependentdistribution we also estimate theoretically. Based on these results, we developa strategy to quantify in silico the statistical errors associated with thedetection of aggregate containing samples. Our work opens a new perspective onthe forecasting of protein aggregation in asymptomatic subjects.

Fluctuations in protein aggregation: Design of preclinical screening for early diagnosis of neurodegenerative disease