Seek and You Shall Find: Is Subclinical Amyloid More Common Than Expected?

A novel hotspot of gelsolin instability triggers an alternative mechanism of amyloid aggregation

“…The A551P variant was identified in a patient presenting, in addition to AGel, another rare amyloidosis caused by a mutant of the transthyretin protein (ATTR-V122I) [30] , [37] . The patient did not have any clinical signs typical of AGel and overall A551P deposition appeared to be responsible for a mild phenotype.…”

“…Possible furin-alternative processes have been suggested for a sporadic form of AGel associated with the deposition of wild-type (WT) GSN, which is resistant to furin proteolysis [36] . Ex vivo mass spectrometry of amyloid deposits from AGel patients carrying the G167R [20] , A551P [30] , [37] and unidentified mutations [19] revealed fragments not corresponding to the 5 and 8 kDa product of furin and MMP proteolysis. It is not yet known whether these peptides originate from alternative proteolytic patterns or from the fragmentation of full-length GSN during the analysis.…”