Million-fold sensitivity enhancement in proteopathic seed amplification assays for biospecimens by Hofmeister ion comparisons

Detection of aggregated proteins in human tissues represents a challenging, yet proven, avenue for diagnosing neurodegenerative diseases. For therapeutic advances to occur, an accurate and early diagnosis must be made, which would ideally rely on a biomarker that can track the progression of the disease. One challenging aspect to this approach is achieving enough sensitivity to detect very low (sometimes attogram, 10^-18 g) amounts of aggregates in diagnostically available tissues. Here, we show that this level of sensitivity can be achieved through optimization of the ionic environment in which these aggregates are amplified through their self-seeding ability. The use of weakly or strongly hydrated anions can enhance the seeded-polymerization-based detection of aggregates from biological tissues, thus potentially enhancing the diagnostic capability of these assays.