Schematic illustration of SP-PLA. (a) Capture antibodies are immobilized on a microparticulate solid support followed by (b) capture of target molecules from the biological sample. (c) Next, the beads are incubated with a pair of PLA probes - that is antibodies with attached oligonucleotides - where after excess probes and other reaction components are removed by washes. (d) Next a cocktail of reagents are added for probe ligation guided by a connector oligonucleotide, and for real-time PCR. (e) After a brief ligation step, (f) ligation products representing detected protofibrils are detected and quantified by real-time PCR.