A Brief History of Amyloidosis

Amyloidoses are disorders due to gene mutations, aging, or systemic diseases leading to the extracellular deposition of fibrillar proteins, which cause morphological and functional alterations of tissues. The term “amyloid” was introduced in the nineteenth century by the German botanist Matthias Schleiden, who firstly used a histochemical staining reaction by iodine and sulfuric acid allowing the detection of starch (ἄμυλον in Greek, “amylum” in Latin) in plants. Then the German physician and physiologist Rudolf Virchow (1821–1902) introduced the term “amyloid” in the medical literature. While Virchow believed that these tissue deposits had the same composition of starch, during the second half of the nineteenth century it was assessed that they are composed of proteins. In 1922, Congo red staining was found to mark amyloid deposits. The reactivity with Congo red staining, i.e., congophilia with apple green birefringence under polarized light was the first diagnostic criterion for amyloid, and it is still relevant for diagnosis. From the second half of the twentieth century, electron microscopy allowed to characterize the ultrastructure of amyloid deposits. Furthermore, a growing number of proteins were identified as possible precursors of amyloid deposits. The most recent and significant developments in the field of amyloidosis are represented by either the introduction of new diagnostic techniques or the identification of therapies interfering with specific steps of the amyloidogenic cascade.